Rescuing Infertility of Pick1 Knockout Mice by Generating Testis-specific Transgenic Mice via Testicular Infection

Abstract

PICK1 (protein interacting with C-kinase 1) is a peripheral membrane protein with high expression in brain, testis, pancreas and other neuroendocrine tissues. Male Pick1 knockout mice are completely infertile, with a phenotype resembling the human disease globozoospermia. Since PICK1 is expressed in both testis and neuroendocrine tissues, infertility of Pick1 knockout mice may be due to either impaired neuroendocrine function or abnormal spermatogenesis. To distinguish these two possibilities, we restored PICK1's expression in the testis by seminiferous tubule microinjection of PICK1-containing lentivirus. By examining the testis-specific Pick1 transgenic mice, we found that PICK1's expression in testis rescued the spermatogenic abnormalities and male infertility in Pick1 knockout mice. Our results indicate that the infertility is caused by the lack of PICK1 in the testis rather than in other organs. In addition, we found that seminiferous tubule microinjection of lentivirus has a strong preference to produce testis-specific transgenic mice.