Sperm-Specific Cation Channel, and Uses Therefor

Abstract

Nucleic acid and protein sequences relating to a cation channel which is sperm-specific (CatSper1) are disclosed. The CatSper1 protein is shown to be specifically expressed in sperm and to be necessary for sperm motility. Nucleic acids, vectors, transformed cells, transgenic animals, polypeptides, and antibodies relating to the CatSper1 gene and protein are disclosed. Also provided are methods of in vitro fertilization and contraception, methods of identifying modulators of CatSper1 activity, methods of genotyping subjects with respect to CatSper1, and methods of diagnosing and treating CatSper1-mediated disorders, including infertility.

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 CatSper1 protein, the CatSper1 protein comprising at least 90% similarity to the amino acid sequence of SEQ ID NO: 4, and wherein the CatSper1 protein has CatSper1 activity. 
     
     
         2 . A transgenic non-human animal comprising a modification into the non-human animal, wherein the modification is replacement of an endogenous CatSper1 protein sequence with a reporter or marker gene, wherein the CatSper1 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 CatSper1 protein, wherein the CatSper1 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 CatSper1 sequences are conspecific to the transgenic animal. 
     
     
         7 . The transgenic non-human animal of any one of  claims 1 - 3 , wherein the CatSper1 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.