# US 7,745,690 B2 · Transgenic nonhuman mammal representing the pathologic conditions of human rheumatoid arthritis

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- Number: US 7,745,690 B2
- Document ID: US7745690B2
- Status: Granted
- Kind: B2
- Application number: 10/591,993
- Filed: 2005-03-08
- Published: 2007-08-23
- Granted: 2010-06-29
- Earliest claimed: 2004-03-09
- Assignees: Nagoya Industrial Science Research Institute
- Inventors: Satoshi Kanazawa; Takashi Okamoto
- Web page: https://patentgrep.com/patent/US7745690B2

## CPC

- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- C07K 14/4702: {Regulators; Modulating activity}
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic)
- A01K 2227/105: Murine
- A01K 2267/0325: Animal model for autoimmune diseases
- 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

It is intended to provide a transgenic nonhuman mammal well representing the pathologic conditions of human rheumatoid arthritis. A transgenic nonhuman mammal is obtained by transferring a foreign DNA, wherein a DNA selected from the group consisting of an MHC class II transcriptional activator gene, the activity domain of an MHC class II transcriptional activator gene and a variant of an MHC class II transcriptional activator gene is provided under the control of a type II collagen promoter, into a cell at the early stage of development.

## Claims

### Claim 1

A transgenic mouse or rat whose genome comprises a foreign DNA, the foreign DNA comprising a type II collagen promoter, a MHC class II transactivator gene, and a type II collagen enhancer sequence, wherein said DNA is located under the control of said type II collagen promoter and enhancer, wherein administration of type II collagen to said transgenic mouse or rat at a dose of 0.01 mg to 0.05 mg two or more times results in presentation of pathologic conditions of human rheumatoid arthritis in said transgenic mouse or rat, wherein the pathologic conditions of human rheumatoid arthritis show the following pathologic conditions (1) to (6):
(1) Joint swelling is observed in the whole body;
(2) Joint swelling lasting for a week or more is observed;
(3) Destruction, ankylosis, or deformity of bones in the extremities is observed;
(4) Infiltration of lymphoid cells is observed;
(5) Cartilage destruction and bone destruction due to formation of granulation tissue are observed; and
(6) Joint deformity progresses through early stage (stage I) and moderate stage (stage II).
