Division of Life Science, Division of Biomedical Engineering and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Sci Rep. 2013 Oct 8;3:2842. doi: 10.1038/srep02842.
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.
PICK1（蛋白相互作用激酶 1）是一种外周膜蛋白，在大脑、睾丸、胰腺和其他神经内分泌组织中高表达。雄性 Pick1 基因敲除小鼠完全不育，表型类似于人类疾病圆头精子症。由于 PICK1 在睾丸和神经内分泌组织中均有表达，Pick1 基因敲除小鼠的不育可能是由于神经内分泌功能障碍或精子发生异常。为了区分这两种可能性，我们通过睾丸生精小管内注射含 PICK1 的慢病毒来恢复 PICK1 在睾丸中的表达。通过检查睾丸特异性 Pick1 转基因小鼠，我们发现 PICK1 在睾丸中的表达挽救了 Pick1 基因敲除小鼠的精子发生异常和雄性不育。我们的结果表明，不育是由于睾丸中缺乏 PICK1 引起的，而不是其他器官。此外，我们发现慢病毒的生精小管内注射具有产生睾丸特异性转基因小鼠的强烈偏好。
