Transgenic animals and uses thereof

• US 7,420,099 B2
• Filed: 04/21/2005
• Issued: 09/02/2008
• Est. Priority Date: 04/22/2004
• Status: Expired due to Fees

• Current Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kirin Holdings Kabushiki Kaisha
• Inventors: Kuroiwa, Yoshimi, Tomizuka, Kazuma, Ishida, Isao, Robl, James M., Kasinathan, Poothappillai
• Primary Examiner(s): Woitach; Joseph
• Assistant Examiner(s): SAJJADI, FEREYDOUN GHOTB
• Application Number:
  US11/111,310
• Publication Number:
  US 20060041945A1
• Time in Patent Office: 1,230 Days
• Field of Search: 800/15, 800/6, 800/25
• US Class Current: 800/15
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/072 maintaining or altering function, i.e. knock in
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/101 Bovine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 2267/02 Animal zootechnically ameliorated
• CPC Class Codes: A01K 2267/0343 Animal model for prion disease
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A01K 67/0273 Cloned vertebrates
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A01K 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• CPC Class Codes: C07K 2317/00 Immunoglobulins specific features
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 15/8771 Bovine embryos

Abstract

In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Claims

1. A transgenic bovine whose genome comprises homozygous mutations of both alleles of two different unrearranged IgM heavy chain loci, said mutations disrupting IgM heavy chain production and said transgenic bovine producing less than 10% of endogenous IgM heavy chain relative to a control bovine lacking the mutations.

2. The transgenic bovine of claim 1, wherein said bovine lacks functional IgM heavy chain.

3. The transgenic bovine of claim 1, wherein at least one mutation is by the insertion of an exogenous sequence, stop codon, or both.

4. A somatic cell obtained from the transgenic bovine of claim 1, whose genome comprises homozygous mutations of both alleles of two different IgM heavy chain loci, said mutations disrupting IgM heavy chain production.

5. The transgenic bovine somatic cell of claim 4, wherein one of said loci is Igμ

U and one of said loci is Igμ

AY.

6. The cell of claim 4, wherein said cell is a B cell.

7. The transgenic bovine of claim 1, wherein one of said loci is Igμ

U.

8. The transgenic bovine of claim 1, wherein one of said loci is Igμ

AY.

9. The transgenic bovine of claim 1, wherein one of said loci is Igμ

U and one of said loci is Igμ

AY.

10. The transgenic bovine somatic cell of claim 4, wherein one of said loci is Igμ

U.

11. The transgenic bovine somatic cell of claim 4, wherein one of said loci is Igμ

AY.

12. The transgenic bovine somatic cell of claim 4, wherein at least one mutation is by the insertion of an exogenous sequence, stop codon, or both.

13. The transgenic bovine of claim 1, wherein said homozygous mutations occur at different positions in said loci.

14. The transgenic bovine of claim 1, wherein said homozygous mutations result from different insertions.

15. The transgenic bovine of claim 1, wherein said homozygous mutations result from insertion of different exogenous sequences, or stop codons, or both.

16. The transgenic bovine of claim 1, wherein said bovine is an adult bovine, fetal bovine, or bovine embryo.

17. The transgenic bovine somatic cell of claim 4, wherein said homozygous mutations occur at different positions in said loci.

18. The transgenic bovine somatic cell of claim 4, wherein said homozygous mutations result from different insertions.

19. The transgenic bovine somatic cell of claim 4, wherein said homozygous mutations result from insertion of different exogenous sequences, or stop codons, or both.