U.S. patent application number 12/528362 was filed with the patent office on 2010-06-03 for compositions and methods for altering gene expression.
This patent application is currently assigned to HILL'S PET NUTRITION, INC.. Invention is credited to Nolan Zebulon Frantz, Kim Gene Friesen, Xiangming Gao, Ryan Michael Yamka, Steven Curtis Zicker.
Application Number | 20100137404 12/528362 |
Document ID | / |
Family ID | 39563552 |
Filed Date | 2010-06-03 |
United States Patent
Application |
20100137404 |
Kind Code |
A1 |
Yamka; Ryan Michael ; et
al. |
June 3, 2010 |
Compositions and Methods for Altering Gene Expression
Abstract
Compositions and methods for regulating gene expression in a
growing animal are disclosed.
Inventors: |
Yamka; Ryan Michael;
(Topeka, KS) ; Friesen; Kim Gene; (Carthage,
IN) ; Zicker; Steven Curtis; (Lawrence, KS) ;
Frantz; Nolan Zebulon; (Topeka, KS) ; Gao;
Xiangming; (Topeka, KS) |
Correspondence
Address: |
COLGATE-PALMOLIVE COMPANY
909 RIVER ROAD
PISCATAWAY
NJ
08855
US
|
Assignee: |
HILL'S PET NUTRITION, INC.
Topeka
KS
|
Family ID: |
39563552 |
Appl. No.: |
12/528362 |
Filed: |
February 22, 2008 |
PCT Filed: |
February 22, 2008 |
PCT NO: |
PCT/US2008/054800 |
371 Date: |
January 19, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60891171 |
Feb 22, 2007 |
|
|
|
Current U.S.
Class: |
514/44A |
Current CPC
Class: |
A61P 3/00 20180101; A61P
3/04 20180101; A23K 20/105 20160501; A61P 43/00 20180101; A23K
20/30 20160501; A61P 31/14 20180101; A61P 33/02 20180101; A61P
25/00 20180101; A61P 31/12 20180101; A61P 37/04 20180101; A61P
31/04 20180101; A23K 20/174 20160501; A23V 2002/00 20130101; A23K
20/158 20160501; A61P 25/28 20180101; A61P 19/00 20180101; A23K
50/40 20160501; A23K 20/142 20160501; A61P 31/20 20180101; A23V
2002/00 20130101; A23V 2200/306 20130101; A23V 2250/0632 20130101;
A23V 2250/1612 20130101; A23V 2250/1868 20130101; A23V 2250/187
20130101; A23V 2250/1872 20130101; A23V 2250/304 20130101; A23V
2250/0644 20130101; A23V 2250/712 20130101; A23V 2250/708 20130101;
A23V 2250/063 20130101; A23V 2002/00 20130101; A23V 2200/30
20130101; A23V 2250/0632 20130101; A23V 2250/1612 20130101; A23V
2250/1868 20130101; A23V 2250/187 20130101; A23V 2250/1872
20130101; A23V 2250/304 20130101; A23V 2250/0644 20130101; A23V
2250/712 20130101; A23V 2250/708 20130101; A23V 2250/063 20130101;
A23V 2250/0612 20130101 |
Class at
Publication: |
514/44.A |
International
Class: |
A61K 48/00 20060101
A61K048/00; A61P 43/00 20060101 A61P043/00 |
Claims
1. A pet food composition comprising: about 5 to about 70% protein,
about 0.5 to about 1.6% methionine, about 50 to about 200 ppm
manganese, about 0.1 to about 0.5% DHA. about 0.1 to about 0.7%
EPA. about 1200 to about 7500 ppm choline, about 1000 to about 2000
ppm taurine, about 2.5 to about 6% linoleic acid, about 1 to about
3% total n-3 fatty acids, about 50 to about 1200 IU/kg vitamin E.
about 50 to about 500 ppm vitamin C, about 50 to about 500 ppm
carnitine, and about 2.5 to about 7 g lysine/1000 kcal.
2. The composition of claim 1 comprising: 0 to about 90% by weight
of carbohydrates: about 20% to about 60% by weight of protein;
about 2% to about 50% by weight of fat; about 0.1% to about 20% by
weight of total dietary fiber; and 0 to about 15% by weight of
vitamins, minerals, and other nutrients
3. The composition of claim 1 comprising about 0.1% to about 0.4%
DHA.
4. The composition of claim 1 comprising about 100 ppm to about 500
ppm carnitine.
5. The composition of claim 1 comprising about 2.5 g/1000 kcal to
about 7 a/1000 kcal lysine.
6. The composition of claim 1 comprising about 0.1% to about 0.6%
EPA.
7. The composition of claim 1 comprising about 50 ppm to about 150
ppm manganese.
8. The composition of claim 1 comprising about 0.8% to about 1.6%
methionine.
9. A method to regulate gene expression in a canine comprising
administering to the canine or to the mother of the canine while
the canine is in utero a composition according to claim 1.
10. The method of claim 9 wherein the canine is a puppy.
11. The method of claim 9 wherein the canine is born of a dam fed
the composition during pregnancy.
12. The method of claim 10 wherein the puppy is in utero.
13. The method of claim 11 wherein the dam is fed the composition
prior to pregnancy.
14. The method of claim 11 wherein the dam is fed the composition
for a majority of the pregnancy duration.
15. The method of claim 11 wherein the dam is fed the composition
prior to and during pregnancy.
16. The method of claim 10 wherein the puppy is fed the composition
prior to weaning.
17. The method of claim 10 wherein the puppy is fed the composition
post weaning.
18. The method of claim 17 wherein the puppy is fed the composition
substantially exclusively.
19. The method of claim 9 wherein an effective amount of the
composition is administered to the canine.
20. The method claim 9 wherein the composition is administered to
the canine for an effective amount of time.
21. The method of claim 20 wherein the composition is administered
to the canine for at least one year post partum or one year post
weaning.
22. The method claim 9 wherein the gene is selected from those
listed in Tables 2-15.
23. A method to cause a beneficial modification in the expression
of any one or more genes provided in Tables 2-5 in an animal, for
any one or more biological conditions, pathways or disease states
described in Tables 2-15, comprising administering an effective
amount of a composition according claim 1 to the animal, either
directly to the animal or to the dam of the animal while the animal
is in utero.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional
Application No. 60/891,171, filed on Feb. 22, 2007, the contents of
which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions and methods
regulating gene expression or transcription in a growing
animal.
BACKGROUND OF THE INVENTION
[0003] Commercially available canine and feline foods include
compositions specially formulated to address many different
nutritional needs. These include, for example, formulations
designed for different breed types, sizes and body conditions. They
also include formulations designed to address the nutritional needs
of animals in the different stages of their life cycle. Typically,
these stages include the growth, adult and senior stages of life.
For example, U.S. Pat. No. 5,851,573 discloses a pet food
composition for large breed puppies; U.S. Pat. No. 6,426,100
discloses compositions to provide improved bone modeling and
chondrocyte functioning in growing animals; U.S. Pat. No. 6,582,752
discloses gender specific puppy food. Despite the availability of
such pet food formulations, however, the need remains for the
development of additional formulations comprising innovative
ingredients and nutrients designed to enhance the development of
growing animals.
[0004] It is known in the art that certain nutrients have an effect
on gene expression. Nutrigenomics is the study of such a
relationship. Despite what is already known, there is a need to
develop compositions and methods which may positively influence
gene expression of an animal.
SUMMARY OF THE INVENTION
[0005] In certain aspects, the present invention relates to
compositions that are useful to enhance the development of a
growing animal. Particularly, the compositions of the present
invention comprise one or more nutrients or bioactive substances
that can enhance neurologic development, bone and joint health,
immune function, and promote healthy body composition in a growing
animal. In certain embodiments, the nutrients and bioactive
substances include, but are not limited to, fatty acids,
antioxidants, essential nutrients, amino acids, minerals and trace
elements, vitamins and vitamin-like substances. Other aspects of
the invention relate to methods to enhance the development of a
growing animal comprising administration of effective amounts of
the compositions of the present invention directly to a growing
animal or to the dam of said animal while the animal is in utero or
is a nursling.
[0006] Thus, in one aspect, the present invention includes
Composition 1.0, a pet food composition comprising:
[0007] about 5 to about 70% protein,
[0008] about 0.5 to about 1.6% methionine,
[0009] about 50 to about 200 ppm manganese,
[0010] about 0.1 to about 0.5% DHA,
[0011] about 0.1 to about 0.7% EPA,
[0012] about 1200 to about 7500 ppm choline,
[0013] about 1000 to about 2000 ppm taurine,
[0014] about 2.5 to about 6% linoleic acid,
[0015] about 1 to about 3% total n-3 fatty acids,
[0016] about 50 to about 1200 IU/kg vitamin E,
[0017] about 50 to about 500 ppm vitamin C,
[0018] about 50 to about 500 ppm carnitine, and
[0019] about 2.5 to about 7 g lysine/1000 kcal.
[0020] The preset invention also includes the following
compositions:
1.1 Composition 1.0 comprising: [0021] 0 to about 90% by weight of
carbohydrates; [0022] about 20% to about 60% by weight of protein;
[0023] about 2% to about 50% by weight of fat; [0024] about 0.1% to
about 20%, by weight of total dietary fiber; and [0025] 0 to about
15% by weight of vitamins, minerals, and other nutrients in varying
percentages which support the nutritional needs of the animal. 1.2
Composition 1.0 or 1.1 comprising about 5% to about 55%, by weight
of carbohydrates; 1.3 Any of the preceding compositions comprising
about 20% to about 50%, by weight of protein, e.g., about 22% to
about 50%; 1.4 Any of the preceding compositions comprising about
5% to about 40%, by weight of fat, e.g., e.g., at least about 8% or
about 9% to about 40% fat; 1.5 Any of the preceding compositions
comprising about 1% to about 11%, by weight of total dietary fiber;
1.6 Any of the preceding compositions comprising about 0.1% to
about 0.4% DHA, e.g., about 0.5%; 61.7 Any of the preceding
compositions comprising about 200 IU/kg to about 1200 IU/kg Vitamin
E, e.g., about 200 IU/kg to about 1000 IU/kg; 1.9 Any of the
preceding compositions comprising about 100 ppm to about 500 ppm
carnitine, e.g., about 200 to about 400, or about 300 ppm; 1.10 Any
of the preceding compositions comprising about 2.5 g/1000 kcal to
about 7 g/1000 kcal lysine; 1.11 Any of the preceding compositions
comprising about 2500 ppm to about 7500 ppm choline, e.g., about
3000, about 3500, about 4000, about 4500, about 4600, about 4625,
about 4650, about 4700, about 4800, or about 6000 ppm; 1.12 Any of
the preceding compositions comprising about 0.1% to about 0.6% EPA;
1.13 Any of the preceding compositions comprising about 50 ppm to
about 150 ppm manganese; and 1.14 Any of the preceding compositions
comprising about 0.8% to about 1.6% methionine.
[0026] In another aspect, the invention relates to methods to cause
a beneficial modification in gene expression in an animal,
specifically, down regulation in expression of a gene or genes
associated with an undesirable biological condition or pathway or
disease state and/or up regulation in expression of a gene or genes
associated with a desired biological condition or pathway or which
may have a positive or preventive effect on a disease state for any
one or more biological conditions, pathways or disease states and
genes described in Tables 2-15, comprising administering an
effective amount of a composition of according to any one of
compositions 1.0-1.14 to an animal, either directly to the animal
or to the dam while the animal is in utero.
[0027] In another aspect, the invention is directed to Method 2.0,
a method to regulate gene expression in a canine comprising
administering to the canine any one of compositions the
compositions of the present invention, e.g., compositions
1.0-1.14.
[0028] The present invention also includes the following methods:
[0029] 2.1 Of method 2.0 wherein the canine is a puppy. [0030] 2.2
Of method 2.0 or 2.1 wherein the canine is born of a dam fed any
one of compositions 1.0-1.14 during pregnancy. [0031] 2.3 Of method
2.2 wherein the puppy is in utero. [0032] 2.4 Of method 2.2 wherein
the dam is fed any one of compositions 1.0-1.14 prior to pregnancy.
[0033] 2.5 Of method 2.2 or 2.4 wherein the dam is fed any one of
compositions 1.0-1.14 for a majority of the pregnancy duration.
[0034] 2.6 Of any one of methods 2.2-2.5 wherein the dam is fed
compositions consisting essentially of any one of compositions
1.0-1.14 prior to and during pregnancy. [0035] 2.7 Of any one of
the preceding methods wherein the puppy is fed any one of
compositions 1.0-1.14 prior to weaning, e.g., while still a
nursling. [0036] 2.8 Of any one of the preceding methods wherein
the puppy is fed any one of compositions 1.0-1.14 post weaning.
[0037] 2.9 Of method 2.8 wherein the puppy is fed food compositions
consisting of any one of compositions 1.0-1.14. [0038] 2.10 Of any
one of the preceding methods wherein an effective amount of the
composition is administered to the canine. [0039] 2.11 Of any one
of the preceding methods wherein the composition is administered to
the canine for an effective amount of time. [0040] 2.12 Of method
2.11 wherein the composition is administered to the canine for at
least one year post partum or one year post weaning. [0041] 2.13 Of
any one of the preceding method wherein the gene is selected from
those listed in Tables 2-15.
[0042] In a further aspects, the invention relates to the use of
any of the formulae of the present invention in the manufacture of
a composition to modify gene expression in an animal as described
herein.
[0043] Other features and advantages of the present invention will
be understood by reference to the detailed description of the
examples that follow.
DETAILED DESCRIPTION OF THE INVENTION
[0044] It is contemplated that the invention described herein is
not limited to the particular methodology, protocols, and reagents
described as these may vary. It is also to be understood that the
terminology used herein is for the purpose of describing particular
embodiments only, and is not intended to limit the scope of the
present invention in any way.
[0045] Unless defined otherwise, all technical and scientific terms
used herein have the same meanings as commonly understood by one of
ordinary skill in the art to which this invention belongs. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls.
[0046] As used herein and in the appended claims, the singular
forms "a", "an", and "the" include plural reference unless the
context clearly dictates otherwise.
[0047] The present invention relates to any animal, preferably a
mammal, more preferably a companion animal. The term "companion
animal" refers to any animal that lives in close association with
humans and includes, but is not limited to, canines and felines of
any breed. It is contemplated herein, however, that any animal
whose diet may be controlled by humans may benefit from feeding the
formulations disclosed herein. These animals may include, for
example, domesticated farm animals (e.g., cattle, horses, swine,
etc.) as well as undomesticated animals held in captivity, e.g., in
zoological parks and the like. Preferred animals include canines,
e.g., dogs, including growing dogs, e.g., puppies.
[0048] "Beneficial modification in the expression of genes" as used
herein includes, e.g., down regulation of genes expressing proteins
associated with disease states and/or up regulation of genes
expressing proteins which have a beneficial or healthful effect as
compared to appropriate controls, as may be determined using
conventional methods, e.g., by microarray (e.g., Affymetrix gene
chip) techniques familiar to one of skill in the art. Further, one
of skill in the art is familiar with the known associations between
diseases and specific genes as those listed in the tables provided
hereinbelow such that it is understood whether an increase or
decrease in expression of a particular gene is desirable.
[0049] The "growth" life stage of an animal refers to the period
from birth or weaning (approximately 8 weeks of age) to about 1
year of age or beyond, depending on the species and breed of the
animal.
[0050] As used herein, the term "puppy" refers to an immature
canine, typically between the ages of birth and 12 months.
[0051] "Essential amino acids" as used herein refers to those amino
acids that cannot be synthesized de novo by an organism and thus
must be supplied in the diet. It is understood by one of skill in
the art that the essential amino acids varies from species to
species, depending upon the organism's metabolism. For example, it
is generally understood that the essential amino acids for dogs and
cats (and humans), are phenylalanine, leucine, methionine, lysine,
isoleucine, valine, threonine, tryptophan, histidine and
arginine.
[0052] As understood by one of skill in the art, a "limiting amino
acid" refers to an amino acid which if present in insufficient
quantities in a diet, results in the limitation in usefulness of
other essential amino acids, even if the other essential amino
acids are present in otherwise large enough quantities. Lysine is
the limiting essential amino acid in the compositions disclosed
herein. Thus, the remaining essential amino acids are
quantitatively formulated or "balanced" in relationship to the
amount of lysine determined critical to affect the desired
biological result. As used herein, "balanced amino acids" refers to
the relationship of the essential amino acid lysine to energy to
assure optimal animal growth and development.
[0053] "Essential nutrients" as used herein refers to nutrients
required for normal body functioning that cannot be synthesized by
the body. Categories of essential nutrient include vitamin dietary
minerals, fatty acid, and amino acid. It is understood by one of
skill in the art that the nutrients deemed essential varies from
species to species, depending upon the organism's metabolism. For
example, essential nutrients for dogs and cats include Vitamins A,
D, E, K, B1, B6 B12, riboflavin, niacin, pantothenic acid, folic
acid, calcium, phosphorous, magnesium, sodium, potassium, chlorine,
iron, copper, zinc, manganese, selenium and iodine. Choline,
generally regarded as a B complex vitamin, may be included among
the semi-essential nutrients. In addition, taurine, while
technically not an amino acid but a derivative of cysteine, is an
essential nutrient for cats.
[0054] Carnitine, also known as L-carnitine, (levocarnitine) is a
quaternary ammonium compound synthesized from the amino acids
lysine and methionine and is responsible for the transport of fatty
acids from the cytosol into the mitochondria.
[0055] Without being limited to any theories or particular modes of
action, the present invention is based on the surprising discovery
that the addition of certain ingredients to pet food compositions
and administration of these compositions to animals can enhance the
development of a growing animal. For example, data indicate that
animals fed the compositions of the present invention (or those
whose dams were fed the compositions during gestation and prior to
weaning but continued throughout growth of their litters),
demonstrate enhanced neurologic development, bone and joint health,
immune function, and have overall healthier body composition.
Interestingly, microarray data also indicate a differential change
in gene expression in these animals compared to controls which is
generally reflective of a beneficial modification (i.e., up or down
regulation) in the expression of many genes associated with
biological processes including those involved in growth and
development. Thus, in one aspect, the invention relates to
compositions and methods to enhance the development of a growing
animal as described in detail herein.
[0056] As contemplated herein, the compositions of the present
invention comprise nutritionally complete and balanced animal feed
compositions. Such compositions include, among other nutrients and
ingredients, recommended healthful amounts of protein, carbohydrate
and fat. "Nutritionally complete and balanced animal feed
compositions", as well as nutrients and ingredients suitable for
animal feed compositions, and recommended amounts thereof, are
familiar to one of skill in the art (see, for example, National
Research Council, 2006 Nutritional Requirements for Dogs and Cats,
National Academy Press, Washington D.C. or the Official Publication
of the Association of American Feed Control Officials, Inc.
Nutrient Requirements for Dogs and Cats 2006).
[0057] It is contemplated herein that the compositions disclosed
herein may also comprise antioxidants, additives, stabilizers,
thickeners, flavorants, palatability enhancers and colorants in
amounts and combinations familiar to one of skill in the art.
"Antioxidants" refers to a substance that is capable of reacting
with or decreasing the production of free radicals and neutralizing
them. Examples include, but are not limited to, beta-carotene,
selenium, coenzyme Q10 (ubiquinone), lutein, tocotrienols, soy
isoflavones, S-adenosylmethionine, glutathione, taurine,
N-acetylcysteine, vitamin E, vitamin D, vitamin C, flavanoids,
anthocyanindins, and lipoic acid.
[0058] While foods of any consistency or moisture content are
contemplated, preferably the compositions of the present invention
may be, for example, a wet, semi-dry, or dry animal food
composition. "Wet" food refers to food which is sold in cans or
foil bags and has a moisture content of about 70 to about a 90%.
"Dry" food refers to compositions with about 5 to about 15%
moisture content and is often manufactured in the form of small
bits or kibbles. Semi-dry compositions refers to food which has a
moisture content greater than dry foods, but less than wet foods.
Also contemplated herein are compositions of intermediate moisture
consistency and those that may comprise components of various
consistency as well as components that may include more than one
consistency, for example, soft, chewy meat-like particles as well
as kibble having an outer cereal component and an inner cream
component as described in, e.g., U.S. Pat. No. 6,517,877.
[0059] Various processes for manufacturing and packaging the
compositions of the present invention may be employed and are
familiar to one of skill in the art.
[0060] It is also contemplated herein that the methods of the
present invention include methods to cause a beneficial
modification in gene expression in an animal, specifically, down
regulation in expression of a gene or genes associated with an
undesirable biological condition or pathway or disease state and/or
up regulation in expression of a gene or genes associated with a
desired biological condition or pathway or which may have a
positive or preventive effect on a disease state, as the case may
be, for any one or more biological conditions, pathways or disease
states and genes described in Tables 14-27, comprising
administering an effective amount of a composition of the present
invention to the animal, either directly to the animal or to the
dam while the animal is in utero. Indeed, as discussed in Examples
7 and 8 here-in-below, by effecting the animal at the genomic
level, the administration of the compositions of the present
invention, either directly to the animal or to the dam while the
animal is in utero, may have beneficial, even prophylatic, health
effects on the animal by effecting the expression of any one or
more genes listed in Tables 14-27. For example, the administration
of an effective amount of a composition of the present invention to
an animal may enhance bone and joint health in the animal by
causing the down regulation in genes associated with cartilage and
joint damage associated with arthritis, e.g. interleukin 1-beta,
fibronectin, lactoransferrin, etc. (see Table 14).
[0061] It is contemplated herein that the compositions of the
present invention may be administered to an animal alone as a
complete nutritionally balanced diet, or in conjunction with
dietary supplements, vitamins and/or other nutritionally beneficial
agents familiar to one of skill in the art, as part of an overall
wellness program for the animal. Compositions of the invention may
also be useful as a veterinary therapeutic product. As such, the
compositions may optionally contain a carrier, diluent, or an
excipient, the suitability of which for the intended use being
familiar to one of skill in the art.
[0062] It is also contemplated that, in addition to administering
the compositions disclosed herein directly to a growing animal,
e.g., to a growing puppy or kitten, the compositions may be
administered to the dam of the animal while the animal is still in
utero or while the animal is a nursling.
[0063] The following examples further illustrate the present
invention and are not intended to limit the invention. As used
throughout, ranges are used as shorthand for describing each and
every value that is within the range. Any value within the range
can be selected as the terminus of the range. It is understood that
when formulations are described, they may be described in terms of
their ingredients, as is common in the art, notwithstanding that
these ingredients may react with one another in the actual
formulation as it is made, stored and used, and such products are
intended to be covered by the formulations described.
[0064] The following examples further describe and demonstrate
illustrative embodiments within the scope of the present invention.
The examples are given solely for illustration and are not to be
construed as limitations of this invention as many variations are
possible without departing from the spirit and scope thereof.
Various modifications of the invention in addition to those shown
and described herein should be apparent to those skilled in the art
and are intended to fall within the appended claims.
[0065] Except to the extent stated otherwise, all percentages used
in this specification are weight percentages on a dry matter basis.
The phrase "dry matter basis" means the component concentration in
the composition after any moisture in the composition is
removed.
EXAMPLES
Example 1
Canine Genetic Effects: Conception to One Year of Age
[0066] In order to characterize the genotypic effects of feeding a
composition formulated to enhance the development of a growing
animal, an experiment is performed to identify changes in gene
expression in puppies at one year of age from dams fed the
compositions disclosed in Table 1.
TABLE-US-00001 TABLE 1 Average of analyzed nutrient profiles of
foods utilized in the study Nutrients, 100% Dry Matter Basis
Composition H Composition P Moisture, % 6.09 7.44 Crude Protein, %
29.4 27.9 Fat, % 17.6 14.2 Ca, % 1.43 1.46 P, % 1.2 0.96 EPA, %
0.31 <0.01 DHA % 0.19 0.01 Linoleic Acid, % 3.8 2.14 Total n-3
fatty acids, % 1.4 0.19 Total n-6 fatty acids, % 3.7 2.6 Taurine, %
0.14 0.08 Carnitine, ppm 312.1 No analysis Methionine, % 1.3 0.52
Cystine, % 0.4 0.39 Manganese, % 94.5 64 Vitamin E, IU/kg 816 43.8
Vitamin C, ppm 168.6 <10 Choline, ppm 4876 No analysis
[0067] Composition P is a commercially available dog food.
Composition H is an experimental dog food composition.
[0068] Dams are fed either Composition H or Composition P for at
least 10 days prior to conception. Dams are maintained in group
lodging until confirmed pregnant via palpation, and are then moved
to maternity lodging. Puppies from dams are kept on the same foods
fed to the dams until one year of age (including pre-weaning and
post-weaning period). Blood samples are then taken from the puppies
and mRNA isolated according to conventional methods. Microarray
assays are performed using the Affymetrix Canine-2 gene chip
according to conventional methods.
[0069] The tables below show the genes grouped by function and the
direction of expression, wherein up regulation in Composition H
("H") vs Composition P ("P") demonstrates increased gene expression
in Composition H fed puppies compared to Composition P fed puppies.
Similarly, down regulation of a gene in the Composition H fed
puppies vs Composition P fed puppies represents decreased gene
expression in puppies fed Composition H relative to those fed
Composition P.
TABLE-US-00002 TABLE 2 Genes associated with arthritis/inflammation
relevant to bone and joints Direction of expression Annotation
Probe H vs P Interleukin 1-beta CfaAffx.11741.1.S1_s_at down
Fibronectin Cfa.3707.1.A1_s_at down v-fos FBJ murine osteo-
Cfa.9039.1.A1_at down sarcoma viral oncogene homolog dual
specificity phosphatase 1 CfaAffx.25714.1.S1_s_at down
Lactotransferrin CfaAffx.21286.1.S1_s_at down compliment component
5a CfaAffx.7180.1.S1_s_at down receptor xanthine dehydrogenase
CfaAffx.9452.1.S1_s_at down Secreted phoshoprotein 1
CfaAffx.15042.1.S1_s_at down
TABLE-US-00003 TABLE 3 Genes associated with DNA replication and
repair Direction of expression Annotation Probe H vs P DNA
fragmentation Interleukin 1-beta CfaAffx.11741.1.S1_s_at down
Fibronectin Cfa.3707.1.A1_s_at down Neuroregulin 1
CfaAffx.10523.1.S1_s_at down Dual specificity phosphatase 1
CfaAffx.25714.1.S1_s_at down Cell death-inducing DFFA-
CfaAffx.28752.1.S1_at down like effector a Proper DNA processing
control Budding uninhibited by Cfa.1559.1.A1_at up benzimidazoles 1
homolog Topoisomerase II alpha Cfa.18946.1.S1_s_at up Kinetochore
associated 2 Cfa.3066.1.S1_s_at up Claspin homolog
CfaAffx.6235.1.S1_s_at up Cyclin B1 CfaAffx.12419.1.S1_s_at up
Cyclin B2 Cfa.11939.1.A1_s_at up Human chromosome
CfaAffx.25509.1.S1_at up condensation protein G Leucine zipper
protein 5 CfaAffx.8781.1.S1_s_at up Kinesin family member 23
Cfa.15293.1.A1_at up Flap structure specific Cfa.1854.1.A1_at up
endonuclease 1
TABLE-US-00004 TABLE 4 Genes associated with cancer Direction of
expression Annotation Probe H vs P Interleukin 1-beta
CfaAffx.11741.1.S1_s_at down Fibronectin Cfa.3707.1.A1_s_at down
v-fos FBJ murine osteosarcoma viral oncogene Cfa.9039.1.A1_at down
homolog dual specificity phosphatase 1 CfaAffx.25714.1.S1_s_at down
compliment component 5a receptor CfaAffx.7180.1.S1_s_at down
xanthine dehydrogenase CfaAffx.9452.1.S1_s_at down cellular
repressor of E1A-stimulated genes 1 Cfa.10558.3.A1_at down
chondroitin sulfate proteoglycan 2 CfaAffx.13597.1.S1_s_at down
transcobalamin II, mycrocytic anemia CfaAffx.19852.1.S1_s_at down
serpin peptidase inhibitor, clade B member 10
CfaAffx.1043.1.S1_s_at down adenomatosis polyposis coli
down-regulated 1 CfaAffx.28621.1.S1_at down six membrane epithelial
antigen of the prostate 2 Cfa.1933.1.S1_at down alanyl
aminopeptidase Cfa.3774.1.A1_s_at down Cancer susceptibility
candidate 5 Cfa.1126.1.S1_at up Paternally expressed 3
Cfa.4482.1.S1_at up Topoisomerase II alpha Cfa.18946.1.S1_s_at up
Tubulin alpha 6 CfaAffx.13667.1.S1_at up Cyclin B1
CfaAffx.12419.1.S1_s_at up Cell division cycle associated 1
CfaAffx.20529.1.S1_at up Cell division cycle 2
CfaAffx.20006.1.S1_at up Ribonucleotide reductase M2 polypeptide
CfaAffx.6059.1.S1_at up Breast cancer anti-estrogen resistance 3
Cfa.651.1.S1_at up Tumor necrosis factor receptor superfamily
CfaAffx.28790.1.S1_at up member 17 Protein kinase C, iota
CfaAffx.22822.1.S1_s_at up
TABLE-US-00005 TABLE 5 Genes associated with cell compromise
Direction of expression Annotation Probe H vs P Interleukin 1-beta
CfaAffx.11741.1.S1_s_at down Fibronectin Cfa.3707.1.A1_s_at down
Neuroregulin 1 CfaAffx.10523.1.S1_s_at down v-fos FBJ murine osteo-
Cfa.9039.1.A1_at down sarcoma viral oncogene homolog dual
specificity phosphatase 1 CfaAffx.25714.1.S1_s_at down compliment
component 5a CfaAffx.7180.1.S1_s_at down receptor xanthine
dehydrogenase CfaAffx.9452.1.S1_s_at down Macrophage receptor with
Cfa.15713.1.A1_s_at down collagenous structure Cyclin B1
CfaAffx.12419.1.S1_s_at up Cell division cycle 2
CfaAffx.20006.1.S1_at up Hemoglobin epsilon 1
CfaAffx.10240.1.S1_s_at up Protein kinase C, iota
CfaAffx.22822.1.S1_s_at up
TABLE-US-00006 TABLE 6 Genes associated with cellular assembly
Direction of expression Annotation Probe H vs P Interleukin 1-beta
CfaAffx.11741.1.S1_s_at down Fibronectin Cfa.3707.1.A1_s_at down
Neuroregulin 1 CfaAffx.10523.1.S1_s_at down chondroitin sulfate
CfaAffx.13597.1.S1_s_at down proteoglycan 2 cholinergic receptor,
Cfa.8414.1.A1_s_at down muscarinic 3 xanthine dehydrogenase
CfaAffx.9452.1.S1_s_at down Macrophage receptor with
Cfa.15713.1.A1_s_at down collagenous structure Cyclin B1
CfaAffx.12419.1.S1_s_at up Cell division cycle 2
CfaAffx.20006.1.S1_at up Leucine zipper protein 5
CfaAffx.8781.1.S1_s_at up Protein kinase C, iota
CfaAffx.22822.1.S1_s_at up Kinesin family member 23
Cfa.15293.1.A1_at up Budding uninhibited by Cfa.1559.1.A1_at up
benzimidazoles 1 homolog Cyclin B2 Cfa.11939.1.A1_s_at up
Topoisomerase II alpha Cfa.18946.1.S1_s_at up Kinetochore
associated 2 Cfa.3066.1.S1_s_at up Cell division cycle
CfaAffx.20529.1.S1_at up associated 1 Human chromosome
CfaAffx.25509.1.S1_at up condensation protein G Kinesin family
member 11 CfaAffx.12118.1.S1_s_at up A kinase (PRKA) anchor
Cfa.10574.1.A1_at up protein 2 thymopioten Cfa.18367.2.S1_s_at
up
TABLE-US-00007 TABLE 7 Genes associated with cell cycle regulation
Direction of expression Annotation Probe H vs P Interleukin 1-beta
CfaAffx.11741.1.S1_s_at down Fibronectin Cfa.3707.1.A1_s_at down
Neuroregulin 1 CfaAffx.10523.1.S1_s_at down v-fos FBJ murine
osteosarcoma viral oncogene Cfa.9039.1.A1_at down homolog
cholinergic receptor, muscarinic 3 Cfa.8414.1.A1_s_at down dual
specificity phosphatase 1 CfaAffx.25714.1.S1_s_at down cellular
repressor of E1A-stimulated genes 1 Cfa.10558.3.A1_at down Cyclin
B1 CfaAffx.12419.1.S1_s_at up Cell division cycle 2
CfaAffx.20006.1.S1_at up Leucine zipper protein 5
CfaAffx.8781.1.S1_s_at up centromere protein F, 350/400ka (mitosin)
CfaAffx.19534.1.S1_at up Breast cancer anti-estrogen resistance 3
Cfa.651.1.S1_at up Budding uninhibited by benzimidazoles 1
Cfa.1559.1.A1_at up homolog Cyclin B2 Cfa.11939.1.A1_s_at up
Topoisomerase II alpha Cfa.18946.1.S1_s_at up Kinetochore
associated 2 Cfa.3066.1.S1_s_at up Cell division cycle associated 1
CfaAffx.20529.1.S1_at up Human chromosome condensation protein G
CfaAffx.25509.1.S1_at up Kinesin family member 11
CfaAffx.12118.1.S1_s_at up thymopioten Cfa.18367.2.S1_s_at up
TABLE-US-00008 TABLE 8 Genes associated with various functions
Direction of expression Annotation Probe H vs P calcyphosine-like
Cfa.21214.1.S1_s_at down ELKS/RAB6 interacting/CAST family member 2
Cfa.21214.1.S1_at down glutamyl tRNA synthetase 2 Cfa.2057.1.A1_at
down Coiled-coil containing domain 3 Cfa.9084.1.A1_at down
chromosome 16 clone RP11-26P10 Cfa.3834.1.S1_at down SAM domain-
and HD domain-containing CfaAffx.13689.1.S1_at down protein 1
AJ420591 Cfa.15196.1.A1_at down family with sequence similarity 46,
member A CfaAffx.5194.1.S1_at down CD1a antigen Cfa.18390.1.S1_s_at
down epidermal dendritic cell marker (CD1a) CfaAffx.17796.1.S1_at
down ANKYRIN MOTIF CfaAffx.6104.1.S1_s_at down RP11-549H3 on
chromosome X Cfa.9597.1.S1_at down La ribonucleoprotein domain
family, member 1 Cfa.14608.1.A1_at down adenomatosis polyposis coli
down-regulated 1 CfaAffx.28621.1.S1_at down Chromosome 3 open
reading frame 21 CfaAffx.20763.1.S1_at down EGF-like module
containing, mucin-like, CfaAffx.28381.1.S1_s_at down hormone
receptor-like 1 acyltransferase like 1 CfaAffx.14833.1.S1_at down
RP11-95J15 from 7 Cfa.6138.1.A1_at down CD8 antigen, beta
polypeptide 2 Cfa.21011.1.S1_at down multimerin 1
CfaAffx.15515.1.S1_s_at down none Cfa.12500.1.A1_at down
Hypothetical protein FLJ21062 Cfa.1933.2.A1_at down normal mucosa
of esophagus specific 1 Cfa.11815.1.A1_at down regulator of
G-protein signalling 7 CfaAffx.24021.1.S1_s_at down Islet cell
auto-antigen 1 Cfa.11691.1.A1_at down normal mucosa of esophagus
specific 1 (NMES1), CfaAffx.851.1.S1_s_at down transcript variant 2
none Cfa.5989.1.A1_s_at down eukaryotic translation initiation
factor 2, subunit Cfa.9060.1.A1_at down 3 gamma Serine/threonine
kinase 17A CfaAffx.21987.1.S1_at down RP11-542F9 on chromosome 6
CfaAffx.21067.1.S1_at up chromosome 20 open reading frame 172
CfaAffx.13625.1.S1_at up RP11-111I12 on chromosome 1
CfaAffx.16431.1.S1_at up BAT2 domain containing 1 Cfa.15064.1.S1_at
up Rho GTPase activating protein 11A CfaAffx.13079.1.S1_s_at up
polo-like kinase 4 CfaAffx.6762.1.S1_s_at up NADH dehydrogenase
(ubiquinone) flavoprotein 3 CfaAffx.16432.1.S1_s_at up 3 BAC
RP11-223L18 Cfa.3066.1.S1_at up par-3 partitioning defective 3
homolog B Cfa.12402.1.S1_a_at up Hypothetical protein MGC24039
Cfa.19506.1.S1_at up immunoglobulin mu heavy chain
CfaAffx.539.1.S1_x_at up origin recognition complex, subunit 1-like
Cfa.8552.1.A1_s_at up RP11-653G16 from 4 CfaAffx.15773.1.S1_at up
abnormal spindle-like microcephaly-associated Cfa.103.1.A1_s_at up
protein Solute carrier family 22 Cfa.10558.2.S1_at up BCSynL32
immunoglobulin lambda light chain CfaAffx.346.1.S1_at up Purinergic
receptor P2Y, G-protein coupled 10 Cfa.1521.1.S1_at up DEP domain
containing 1 CfaAffx.31279.1.S1_at up chromosome 17, clone
RP11-160L11 Cfa.16355.1.S1_at up Hypothetical protein LOC644115
Cfa.15220.2.A1_at up isolate MRPS17P1 mitochondrial ribosomal
Cfa.12402.1.S1_s_at up protein S17 KIAA0101 (L5)
CfaAffx.26141.1.S1_s_at up chromosome 13 open reading frame 3
CfaAffx.11656.1.S1_at up SHC SH2-domain binding protein 1
CfaAffx.6499.1.S1_at up CDC20 cell division cycle 20 homolog
CfaAffx.8850.1.S1_s_at up Chromosome 14 open reading frame 32
CfaAffx.23135.1.S1_s_at up 3-oxoacyl-ACP synthase, mitochondrial
Cfa.10049.1.A1_s_at up MAD2 mitotic arrest deficient-like 1
CfaAffx.25205.1.S1_s_at up thioredoxin domain containing 5
Cfa.10753.1.A1_at up Apla tubulin Cfa.6991.1.A1_at up none
CfaAffx.32.1.S1_at up Melanin-concentrating hormone receptor 1
Cfa.6032.1.A1_at up Aquaporin 7 Cfa.21549.1.S1_s_at up cathepsin E
CfaAffx.15966.1.S1_at up EF hand domain (C-terminal) containing 2
Cfa.1885.1.A1_at up bone morphogenetic protein 6 Cfa.15702.1.S1_at
up hemoglobin, alpha 2 Cfa.3973.2.A1_s_at up SH3-domain GRB2-like 3
Cfa.10644.1.A1_at up Acidic nuclear phosphoprotein 32 family,
Cfa.31.1.S1_s_at up member A none CfaAffx.20953.1.S1_x_at up Rh
family, B glycoprotein Cfa.13613.1.A1_at up putative protein STRF8
CfaAffx.15063.1.S1_s_at up fatty acid desaturase 1
Cfa.13257.1.A1_at up Ligand dependent nuclear receptor corepressor-
Cfa.1476.1.A1_at up like F-box only protein 2 CfaAffx.9335.1.S1_at
up Ring finger protein 152 Cfa.15414.1.A1_at up immunoglobulin
lambda constant 1 CfaAffx.22878.1.S1_at up G-protein coupled
receptor 158 Cfa.9162.1.A1_at up Hypothetical protein MGC42105
CfaAffx.28387.1.S1_at up
[0070] Gene expression profiles from puppies fed Composition H and
P are obtained and compared. Results indicate that 143 genes are
differentially expressed between the study groups and, in general,
their functions may be associated with cell assembly, cell cycle
regulation, DNA replication and repair, cell compromise, arthritis
and cancer. At a minimum of 1.5 fold change, 143 genes are
differentially expressed in the two groups.
[0071] Genes associated with arthritis/inflammation are
down-regulated in puppies fed Composition H compared to puppies fed
Composition P, which suggests reduced cartilage/joint damage in
Prototype pups. A separate study performed also indicates that
levels of bone alkaline phosphatase are lower in puppies fed
composition H (data not shown). See Table 2.
[0072] Genes associated with DNA fragmentation are down-regulated
and genes associated with DNA processing control are up-regulated
in puppies fed Composition H compared to puppies fed Composition P,
which suggests reduced DNA damage and improved DNA protection in
Prototype pups (also supported by elevated Vitamin E levels in
blood, data not shown). See Table 3.
[0073] Genes associated with cancer incidence are down-regulated
and genes associated with tumor suppression are up-regulated in
puppies fed Composition H compared to puppies fed Composition P,
which suggests the possibility of reduced cancer susceptibility in
these Prototype animals; see Table 4.
[0074] Genes associated with cellular compromise are down-regulated
and genes associated with cellular integrity are up-regulated in
puppies fed Composition H compared to puppies fed Composition P,
which suggests the possibility of reduced cell damage and enhanced
cellular protection in these Prototype animals (also supported by
elevated Vitamin E levels in blood, data not shown). See Table
5.
[0075] Genes associated with disruption of cellular assembly are
down-regulated and genes associated with proper cellular
organization are up-regulated in puppies fed Composition H compared
to puppies fed Composition P, which suggests improved cellular
organization and function in Prototype pups. See Table 6.
[0076] Genes associated with proper cell cycle regulation are
up-regulated and genes associated with disruption of cell cycle
control are down-regulated in puppies fed Composition H compared to
puppies fed Composition P, which suggests proper control of cell
cycle progression and cell survival. See Table 7.
[0077] Thus, it is contemplated herein that the nutritional
benefits of the compositions of the present invention as described
herein may involve modification in gene expression which results in
the enhancement of the development of a growing animal. In
addition, feeding proper nutrients during early development may
have a prophylatic effect and influence disease processes later in
life, i.e., lessen the chance of disease in the animal, as the
expression of genes associated with common diseases and disorders
may be influenced due to the given nutritional compositions of the
foods provided maternally and during early development.
Example 2
[0078] An experiment is performed to determine the effects on gene
expression in puppies fed Composition H vs. Composition P from
weaning until one year of age.
[0079] Dams utilized in this study are fed Composition P prior to,
and during pregnancy. Following weaning, puppies are divided into
two groups and provided with either Composition H or maintained on
Composition P until one year old. Blood samples are then taken from
the puppies and mRNA isolated according to conventional methods.
Microarray assays are performed using the Affymetrix Canine-2 gene
chip according to conventional methods.
[0080] Results indicate that 99 genes are differentially expressed
between the two study groups, and are presented in Tables 9-15. Of
the genes identified, many are related to biological functions or
pathways such as, e.g., immune activation, lipid metabolism,
cardiovascular development, skeletal and muscular disorders,
contraction and function and cell compromise and cancer.
TABLE-US-00009 TABLE 9 Genes associated with immune activation
Direction of expression Annotation Probe H v. P lymphocyte antigen
6 CfaAffx.1839.1.S1_at down complex Fc fragment of IgG, receptor,
Cfa.17806.2.S1_s_at up transporter, alpha fibrinogen-like 2
Cfa.10303.1.S1_at down CD1A antigen Cfa.18390.1.S1_s_at down
complement factor D (adipsin) Cfa.21381.1.S1_s_at down CD163
antigen; macrophage- Cfa.9647.1.A1_at down associated antigen
toll-like receptor 2 CfaAffx.13248.1.S1_s_at down lysozyme (renal
amyloidosis) CfaAffx.1598.1.S1_s_at down transcription elongation
factor Cfa.12580.1.S1_s_at down A (SII), 3 fibronectin 1
Cfa.3707.2.S1_at down macrophage receptor with Cfa.15713.1.A1_s_at
down collagenous structure bactericidal/permeability-
CfaAffx.14056.1.S1_s_at down increasing protein T cell receptor
alpha locus Cfa.10333.1.A1_at down immunoglobulin heavy
Cfa.4556.3.A1_a_at down constant alpha 2 nuclear factor I/B
Cfa.4487.1.S1_at up
TABLE-US-00010 TABLE 10 Genes associated with Cancer formation
Direction of expression Annotation Probe P vs C fibronectin 1
Cfa.3707.3.S1_s_at down xanthine dehydrogenase
CfaAffx.9452.1.S1_s_at down neuregulin 1 CfaAffx.10523.1.S1_s_at
down colony stimulating factor 1 CfaAffx.27899.1.S1_at down
receptor alanyl aminopeptidase Cfa.3774.1.A1_s_at down S100 calcium
binding protein CfaAffx.22128.1.S1_at down dystroglycan 1
CfaAffx.17467.1.S1_at up
TABLE-US-00011 TABLE 11 Genes associated with Lipid metabolism
Direction of expression Annotation Probe H v. P Toll-like receptor
2 CfaAffx.13248.1.S1_s_at Down cytochrome P450, family 1,
CfaAffx.10229.1.S1_at Down subfamily B, polypeptide 1 colony
stimulating factor 1 CfaAffx.27899.1.S1_at Down receptor
phospholipase C, beta 1 Cfa.10853.1.A1_at Down fibronectin 1
Cfa.3707.3.S1_s_at Down neuregulin 1 CfaAffx.10523.1.S1_s_at Down
macrophage receptor with Cfa.15713.1.A1_at Down collagenous
structure CD1a molecule Cfa.18390.1.S1_s_at Down
TABLE-US-00012 TABLE 12 Genes associated with Cardiovascular
development Direction of expression Annotation Probe H v. P
bactericidal/permeability- CfaAffx.14056.1.S1_s_at Down increasing
protein fibronectin 1 Cfa.3707.3.S1_s_at Down neuregulin 1
CfaAffx.10523.1.S1_s_at Down xanthine dehydrogenase
CfaAffx.9452.1.S1_s_at Down annexin A6 CfaAffx.27471.1.S1_s_at Down
colony stimulating factor 1 CfaAffx.27899.1.S1_at Down receptor
alanyl (membrane) Cfa.3774.1.A1_s_at Down aminopeptidase
TABLE-US-00013 TABLE 13 Genes associated with Skeletal/Muscular
disorders and contraction/function Direction of expression
Annotation Probe H v. P Skeletal/Muscular disorders Toll-like
receptor 2 CfaAffx.13248.1.S1_s_at down colony stimulating factor 1
CfaAffx.27899.1.S1_at down receptor fibronectin 1
Cfa.3707.3.S1_s_at down neuregulin 1 CfaAffx.10523.1.S1_s_at down
Muscle contraction/function exostoses Cfa.11001.1.A1_at up
microfibrillar associated CfaAffx.21449.1.S1_s_at up protein 5
myosin light polypeptide Cfa.13192.1.S1_at up kinase dystroglycan 1
CfaAffx.17467.1.S1_at up Moloney leukemia virus
CfaAffx.1982.1.S1_s_at up 10-like 1
TABLE-US-00014 TABLE 14 Genes associated with Cellular Compromise
Direction of expression Annotation Probe H v. P neuroregulin 1
CfaAffx.10523.1.S1_s_at down fibronectin 1 Cfa.3707.3.S1_s_at down
macrophage receptor with Cfa.15713.1.A1_at down collagenous
structure xanthine dehydrogenase CfaAffx.9452.1.S1_s_at down
bactericidal permeability CfaAffx.14056.1.S1_s_at down increasing
protein phospholipase C, beta 1 Cfa.10853.1.A1_at down hemoglobin
epsilon 1 CfaAffx.10240.1.S1_s_at up
TABLE-US-00015 TABLE 15 Genes associated with various functions
Direction of expression Annotation Probe H v. P CCR4-NOT
transcription complex, subunit 10 Cfa.2403.1.A1_at up ubiquitin
carboxy-terminal hydrolase L5 Cfa.20277.1.S1_at up SH3-domain
GBR2-like 3 Cfa.10644.1.A1_at up DEAH (Asp-Glu-Ala-His) box
polypeptide 8 CfaAffx.22452.1.S1_s_at up Signal-induced
proliferation-associated 1 like 2 Cfa.14345.1.A1_at up Cathepsin E
CfaAffx.15966.1.S1_at up ephrin-B3 Cfa.15231.1.A1_at up Fc fragment
of IgG, receptor, transporter, alpha Cfa.17806.2.S1_s_at up
Chromosome 20 open reading frame 172 Cfa.9662.1.A1_at up
Inositol(myo)-1(or 4) monophosphatase 2 Cfa.13029.1.A1_at up
Ferrochelatase (protoporphyria) Cfa.365.3.A1_x_at up G-protein
coupled receptor 158 Cfa.9162.1.A1_at up dual specificity
phosphatase 19 CfaAffx.22249.1.S1_at up Ring finger protein 152
Cfa.15414.1.A1_at up Chromosome 12 open reading frame 49
Cfa.11298.1.S1_at up hemoglobin, epsilon 1 CfaAffx.10240.1.S1_s_at
up Crystallin lambda 1 Cfa.4354.1.S1_a_at up Sorting nexin 6
Cfa.10261.1.S1_at up microfibrillar associated protein 5
CfaAffx.21449.1.S1_s_at up coiled-coil domain containing 46
CfaAffx.17557.1.S1_s_at up Nuclear factor I/B Cfa.4487.1.S1_at up
carboxypeptidase A3 CfaAffx.13076.1.S1_at up chromosome 18, clone
RP11-396D4 CfaAffx.26602.1.S1_at up coxsackie and adenovirus
receptor protein CfaAffx.13148.1.S1_at up WW domain containing
oxidoreductase, transcript Cfa.9201.1.A1_at up variant 4 EH domain
binding protein 1-like 1 Cfa.17641.1.S1_s_at Down RP4-760G15 on
chromosome 11p13 Cfa.17214.1.S1_at Down phospholipase C beta 1
(phosphoinositide-Specific) Cfa.10853.1.A1_at Down cathepsin L
CfaAffx.2868.1.S1_at Down Transcription elongation factor A, 1
Cfa.12580.1.S1_s_at Down glypican 6 Cfa.9523.1.A1_at Down
Hypothetical protein FLJ21062 Cfa.1933.2.A1_at Down G-protein
coupled receptor 101 CfaAffx.12632.1.S1_at Down Leucine-rich repeat
kinase 2 CfaAffx.15613.1.S1_s_at Down Six transmembrane epithelial
anitgen of the Cfa.9430.1.A1_at Down prostate 2 KIAA1074 protein
Cfa.12143.1.A1_at down LOC284395 Cfa.4802.1.S1_at down elastin
microfibril interfacer 2 CfaAffx.28185.1.S1_at down Sulfatase 2
CfaAffx.17034.1.S1_s_at down IBR domain containing 2
Cfa.1882.1.A1_at down Leucyl/cystinyl aminopeptidase
CfaAffx.12483.1.S1_s_at down acyltransferase like 1
CfaAffx.14833.1.S1_at down NAD kinase CfaAffx.29324.1.S1_at down
Immunoglobulin heavy constant alpha 2 Cfa.4556.3.A1_x_at down
transcription factor EC (TFEC), transcript Cfa.1175.1.A1_s_at down
variant 2 Acyl-CoA synthetase short-chain family
CfaAffx.12483.1.S1_at down member 1 Syntaxin binding protein 6
Cfa.9054.1.A1_at down Opioid growth factor receptor-like 1
Cfa.583.1.S1_at down None Cfa.10106.1.A1_at down None
Cfa.4556.3.A1_s_at down ELK/RAB6-interacting/CAST family member 2
Cfa.21214.1.S1_at down adipsin/complement factor D precursor
Cfa.21381.1.S1_s_at down Hypothetical protein FLJ22662
CfaAffx.20271.1.S1_at down solute carrier family 2 (facilitated
glucose Cfa.7132.1.A1_at down transporter), member 9 Homogentisate
1,2 dioxygenase CfaAffx.9076.1.S1_s_at down serpin peptidase
inhibitor, clade B (ovalbumin), CfaAffx.1043.1.S1_s_at down member
10 None Cfa.13203.1.S1_at down Fibrinogen-like 2
CfaAffx.7369.1.S1_s_at down None Cfa.12500.1.A1_at down None
Cfa.4556.2.S1_s_at down None Cfa.4555.1.S1_s_at down None
Cfa.280.1.S1_at down Lymphocyte antigen 6 CfaAffx.1839.1.S1_at down
Neuronal PAS domain protein 3 Cfa.12905.1.A1_a_at down
[0081] Gene expression profiles from puppies fed Composition H or P
from weaning to one year of age are obtained and compared.
Microarray data indicate that, at a minimum of 1.5 fold change, 99
genes are differentially expressed in the two study groups.
[0082] Genes associated with immune activation are down-regulated
in puppies fed Composition H when compared to puppies fed
Composition P, which suggests improved immune system function
(Table 9).
[0083] Genes associated with lipid metabolism are down-regulated in
puppies fed Composition H when compared to puppies fed Composition
P, which suggests reduced lipid processing (Table 11).
[0084] Genes associated with cardiovascular development are also
down-regulated in puppies fed Composition H when compared to
puppies fed Composition P, which suggests enhanced cardiovascular
health (Table 12).
[0085] Genes associated with skeletal muscular disorders are
down-regulated and genes associated with muscle
contraction/function are up-regulated in puppies fed Composition H
when compared to puppies fed Composition P, which suggests reduced
skeletal disorder risk and improved muscle contraction (Table
13).
[0086] Genes associated with cellular compromise are down-regulated
in puppies fed Composition H when compared to puppies fed
Composition P, which suggests reduced cellular damage (Table
14).
[0087] Genes known to have an association with cancer are
down-regulated in puppies fed Composition H when compared to
puppies fed Composition P, which may suggest reduced cancer
susceptibility. (Table 10).
[0088] As discussed above, genetic data such as these indicate that
the nutritional benefits of the compositions of the present
invention include the beneficial modification of gene expression in
the animal such that there is an overall enhancement in the
development of the animal. In addition, the beneficial modification
of gene expression may also result in a decrease in the incidence
of disease in the animal due to an inhibition in expression of
disease related genes and/or an increase in the expression of genes
which play a role in disease prevention.
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