CONTROL OF SEXUAL MATURATION IN ANIMALS

• US 20140123330A1
• Filed: 10/30/2013
• Published: 05/01/2014
• Est. Priority Date: 10/30/2012
• Status: Abandoned Application

• Current Assignee: Recombinetics, Inc, The Center For Aquaculture Technologies, Inc.
• Original Assignee: Recombinetics, Inc
• Inventors: Carlson, Daniel F., Fahrenkrug, Scott C., Lauth, Xavier
• Application Number:
  US14/067,634
• Publication Number:
  US 20140123330A1
• Time in Patent Office: Days
• US Class Current: 800/15
• 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 2227/108 Swine
• CPC Class Codes: A01K 2227/40 Fish
• CPC Class Codes: A01K 2267/02 Animal zootechnically ameliorated
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: C12N 15/8778 Swine embryos
• CPC Class Codes: C12N 15/907 in mammalian cells

Abstract

A genetically modified livestock animal comprising a genome that comprises inactivation of a neuroendocrine gene selective for sexual maturation, with the inactivation of the gene preventing the animal from becoming sexually mature. Methods of using, and processes of making, the animals are taught.

Claims

1. A genetically modified livestock animal comprising a genome that comprises inactivation of a neuroendocrine gene selective for sexual maturation, with the inactivation of the gene preventing the animal from becoming sexually mature.

2. The livestock animal of claim 1 wherein the inactivation of the gene comprises

an insertion, deletion, or substitution of one or more bases in

a sequence encoding the sexual maturation gene and/or a cis-regulatory element thereof.

3. The livestock animal of claim 1 wherein the gene is inactivated by the trans-acting factor, said trans-acting factor being chosen from the group consisting of interfering RNA and a dominant negative factor, with said trans-acting factor being expressed by an exogenous gene or an endogenous gene.

4. The livestock animal of claim 1 wherein the inactivation of the gene is under control of an inducible system.

5. The livestock animal of claim 1 wherein the animal is chosen from the group consisting of cattle, swine, sheep, chicken, goats, and fish.

6. The livestock animal of claim 1 wherein the sexual maturation gene is chosen from the group consisting of Gpr54, Kiss1, and GnRH11.

7. The livestock animal of claim 1 wherein the animal further expresses an exogenous recombinant protein.

8. The livestock animal of claim 1 being genetically unable to mature without a treatment.

9. A genetically modified livestock animal comprising a genome that is heterozygous for an inactivation of a neuroendocrine gene selective for sexual maturation, wherein progeny homozygous for the inactivated gene are thereby prevented from becoming sexually mature.

10. The animal of claim 9 wherein the neuroendocrine gene is chosen from the group consisting of Gpr54, Kiss1, and GnRH11.

11. An in vitro organism chosen from the group consisting of a cell or an embryo, the in vitro organism comprising a genome that comprises an inactivation of a sexual maturation gene.

12. The organism of claim 11 being a cell or embryo chosen from the group consisting of cattle, swine, sheep, chicken, goats, rabbit, and fish.

13. The organism of claim 11 wherein the inactivation is in a gene chosen from the group consisting of Gpr54, KiSS1, and GnRH11.

14. A process of making a livestock animal comprising

introducing, into an organism chosen from the group consisting of a livestock cell and a livestock embryo, an agent that specifically binds to a chromosomal target site of the cell and causes a double-stranded DNA break to inactivate a neuroendocrine gene selective for sexual maturation, with the agent being chosen from the group consisting of a TALEN, a zinc finger nuclease, Cas9/CRISPR and a recombinase fusion protein.

15. The process of claim 14 comprising co-introducing a recombinase into the organism with a TALEN.

16. The process of claim 14 wherein a transgene expressing the agent is placed in a genome of the organism.

17. The process of claim 16 wherein the agent is the recombinase fusion protein, with the process comprising introducing a targeting nucleic acid sequence with the fusion protein, with the targeting nucleic acid sequence forming a filament with the recombinase for specific binding to the chromosomal site.

18. The process of claim 14 further comprising introducing a nucleic acid template having a sequence into the organism, with the genome of the organism at a site of the double-stranded break receiving the sequence.

19. The process of claim 14 further comprising cloning the animal from the organism.

20. The process of claim 14 wherein the animal is chosen from the group consisting of cattle, swine, sheep, chicken, goats, rabbit, and fish.

21. The process of claim 14 wherein the sexual maturation gene is chosen from the group consisting of Gpr54, Kiss1, and GnRH11.

22. The process of claim 14 wherein the inactivation of the gene is under control of an inducible system.

23. A process of raising a livestock animal comprising

administering an agent to an animal for sexual maturation of the animal, with the agent compensating for a genetic inability of the animal to sexually mature.

24. The process of claim 23 wherein the agent comprises a gonadotropin or a gonadotropin analogue.

25. The process of claim 23 wherein the genetic inability of the animal to mature is a result of a genetically inactivated neuroendocrine gene selective for sexual maturation.

26. The process of claim 25 wherein the inactivated gene is chosen from the group consisting of Gpr54, Kiss1, and GnRH11.