# US 2008/0189799 A1 · Genetically engineered and phenotyped mice and stem cell clones for producing the same

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- Number: US 2008/0189799 A1
- Document ID: US20080189799A1
- Status: Published application
- Kind: A1
- Application number: 11/978,234
- Filed: 2007-10-26
- Published: 2008-08-07
- Earliest claimed: 1999-07-20
- Inventors: Liangfen Fan; Glenn Friedrich; Laurie Jeanette Minze; Charles Montgomery; Bobby Joe Payne; Carolina Rangel; Arthur T. Sands; Tracy Ellen Willis Sevaux; Zheng-Zheng Shi; Mary Jean Sparks; Peter Vogel; Brian Zambrowicz
- Web page: https://patentgrep.com/patent/US20080189799A1

## CPC

- A01K 67/0276: Knock-out vertebrates
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 14/7151: {for tumor necrosis factor [TNF], for lymphotoxin [LT]}
- C07K 14/775: Apolipopeptides
- C07K 14/8114: {Kunitz type inhibitors}
- C07K 14/8121: {Serpins}
- C12N 9/1051: {Hexosyltransferases (2.4.1)}
- C12N 9/12: transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N 9/1205: {Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases}
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2267/03: Animal model, e.g. for test or diseases
- C12N 2799/027: where the vector is derived from a retrovirus
- C12N 2800/60: Vectors containing traps for, e.g. exons, promoters
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The current invention relates to genetically engineered mice, cells derived from those mice, and polynucleotides and polypeptides corresponding to genes affected by the engineered mutation. The invention also relates to antibodies raised in a mouse of the invention. The invention further provides methods for using the mice, cells, polynucleotides, polypeptides and antibodies of the invention.

## Claims

### Claim 1

A transgenic mouse whose genome comprises a disruption of a gene and wherein said disruption results in a phenotype that differs form the phenotype of a wild-type mouse, said gene selected from the group consisting of:
a. a gene comprising SEQ ID NO:9, wherein the disruption of the gene comprising SEQ ID NO:9 results in decreased depressive-like response in (−/−) mice;
b. a gene comprising SEQ ID NO:10, wherein the disruption of the gene comprising SEQ ID NO:10 results increased artery-to-vein ratios in (−/−) mice;
c. a gene comprising SEQ ID NO:11, wherein the disruption of the gene comprising SEQ ID NO:11 results in infertile female (−/−) mice exhibiting ovarian hypoplasia;
d. a gene comprising SEQ ID NO:12, wherein the disruption of the gene comprising SEQ ID NO:12 results in an increased percentage of natural killer cells in (−/−) mice;
e. a gene comprising SEQ ID NO:14, wherein the disruption of the gene comprising SEQ ID NO:14 results in a decreased percentage of CD8 cells and an increased percentage of B cells in the peripheral blood of (−/−) mice;
f. a gene comprising SEQ ID NO:15, wherein the disruption of the gene comprising SEQ ID NO:15 results in compensated hemolytic anemia in (−/−) mice;
g. a gene comprising SEQ ID NO:16, wherein the disruption of the gene comprising SEQ ID NO:16 results in decreased bone mineral content and density in (−/−) mice;
h. a gene comprising SEQ ID NO:17, wherein the disruption of the gene comprising SEQ ID NO:17 results in decreased red blood cell count in (−/−) mice;
i. a gene comprising SEQ ID NO:18, wherein the disruption of the gene comprising SEQ ID NO:18 results in an increased percentage of NK cells in (−/−) mice;
j. a gene comprising SEQ ID NO:19, wherein the disruption of the gene comprising SEQ ID NO:19 results in increased serum IgG1 and IgG2a responses to ovalbumin challenge in (−/−) mice;
k. a gene comprising SEQ ID NO:20, wherein the disruption of the gene comprising SEQ ID NO:20 results in enhanced learning/memory in male (−/−) mice;
l. a gene comprising SEQ ID NO:21, wherein the disruption of the gene comprising SEQ ID NO:21 results in small male (−/−) mice, exhibiting a decreased fasting serum glucose level;
m. a gene comprising SEQ ID NO:22, wherein the disruption of the gene comprising SEQ ID NO:22 results in impaired sensorimotor gating/attention in (−/−) mice;
n. a gene comprising SEQ ID NO:23, wherein the disruption of the gene comprising SEQ ID NO:23 results in immunological abnormalities in (−/−) mice;
o. a gene comprising SEQ ID NO:24, wherein the disruption of the gene comprising SEQ ID NO:24 results in decreased pain response in (−/−) mice; and
p. a gene comprising SEQ ID NO:25, wherein the disruption of the gene comprising SEQ ID NO:25 results in increased serum glucose levels in (+/−) and (−/−) animals.

### Claim 2 (depends on 1)

A mouse, said mouse being off-spring of a mouse according to claim 1.

### Claim 3 (depends on 1)

An isolated cell, said cell being derived from a mouse according to claim 1.

### Claim 4 (depends on 3)

The cell according to claim 3, said cell being selected from the group consisting of a stem cell, an embryonic stem cell, a hematopoietic stem cell, a progenitor cell, a fibroblast, a nerve cell, a muscle cell, an epithelial cell, and a teratocarcinoma cell.

### Claim 5 (depends on 1)

An isolated antibody, said antibody being prepared by introducing an antigen into a mouse according to claim 1.

### Claim 6 (depends on 5)

An isolated antibody, said antibody being derived from an antibody according to claim 5 and said antibody being selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a multispecific antibody, a human antibody, a humanized antibody, a chimeric antibody, a single chain antibody, a Fab fragment, a F(ab′) fragment, a fragment produced by a Fab expression library, an anti-idiotypic (anti-Id) antibody, and an epitope-binding fragments of an antibody.