Sperm-specific cation channel, catsper4, and uses therefor

Abstract

Nucleic acid and protein sequences relating to a cation channel which is sperm-specific (CatSper4) are disclosed. The CatSper4 protein is shown to be specifically expressed in sperm. Nucleic acids, vectors, transformed cells, transgenic animals, polypeptides, and antibodies relating to the CatSper4 gene and protein are disclosed. Also provided are methods of in vitro fertilization and contraception, methods of identifying modulators of CatSper4 activity, methods of genotyping subjects with respect to CatSper4, and methods of diagnosing and treating CatSper4-mediated disorders, including infertility. Related business methods are also disclosed.

We claim: 
     
         1 . A transgenic non-human animal comprising a modification into the non-human animal, the modification comprising an insertion of a nucleic acid encoding a CaSper4 protein, the CatSper4 protein comprising at least 90% similarity to the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4, and wherein the CatSper4 protein has CatSper4 activity. 
     
     
         2 . A transgenic non-human animal comprising a modification into the non-human animal, wherein the modification is replacement of an endogenous CatSper4 protein sequence with a reporter or marker gene, wherein the CatSper4 protein comprises at least 90% similarity to the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4. 
     
     
         3 . A transgenic non-human animal comprising a modification into the non-human animal, the modification comprising inactivation of an endogenous CatSper4 protein, wherein the CatSper4 protein comprises at least 90% similarity to the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4. 
     
     
         4 . The transgenic non-human animal of  claim 2 , wherein the modification is by homologous recombination to result in expression of the reporter gene. 
     
     
         5 . The transgenic non-human animal of  claim 2 , wherein the modification is by homologous recombination to result in expression of the marker gene. 
     
     
         6 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the CatSper4 sequences are conspecific to the transgenic animal. 
     
     
         7 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the CatSper4 sequences are transpecific to the transgenic animal. 
     
     
         8 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the animal is a mouse, rat, hamster, guinea pig, rabbit, dog, cat, goat, sheep, pigs, or a non-human primate. 
     
     
         9 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the animal is a mouse. 
     
     
         10 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the animal is a non-human primate.