Sperm-Specific Cation Channel, Catsper3, and Uses Therefor

Abstract

Nucleic acid and protein sequences relating to a cation channel which is sperm-specific (CatSper3) are disclosed. The CatSper3 protein is shown to be specifically expressed in sperm. Nucleic acids, vectors, transformed cells, transgenic animals, polypeptides, and antibodies relating to the CatSper3 gene and protein are disclosed. Also provided are methods of in vitro fertilization and contraception, methods of identifying modulators of CatSper3 activity, methods of genotyping subjects with respect to CatSper3, and methods of diagnosing and treating CatSper3-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 CatSper3 protein, the CatSper3 protein comprising at least 90% similarity to the amino acid sequence of SEQ ID NO: 4, and wherein the CatSper3 protein has CatSper3 activity. 
     
     
         2 . A transgenic non-human animal comprising a modification into the non-human animal, wherein the modification is replacement of an endogenous CatSper3 protein sequence with a reporter or marker gene, wherein the CatSper3 protein comprises at least 90% similarity to the amino acid sequence of 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 CatSper3 protein, wherein the CatSper3 protein comprises at least 90% similarity to the amino acid sequence of SEQ ID NO: 4. 
     
     
         4 . The transgenic non-human animal of  claim 1 , wherein the modification is by homologous recombination to result in expression of the reporter gene. 
     
     
         5 . The transgenic non-human animal of  claim 1 , 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 CatSper3 sequences are conspecific to the transgenic animal. 
     
     
         7 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the CatSper3 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.