Rescuing infertility of Pick1 knockout mice by generating testis-specific transgenic mice via testicular infection.

Rescuing infertility of Pick1 knockout mice by generating testis-specific transgenic mice via testicular infection.
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DOI:
10.1038/srep02842
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发表时间:
2013-10-08
期刊:
影响因子:
4.6
通讯作者:
Xia J
Xia J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li X;Mao Z;Wu M;Xia J

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PICK1(与C激酶1相互作用的蛋白)是一种外周膜蛋白,在脑、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,其表型类似于人类疾病球精子症。由于PICK1在睾丸和神经内分泌组织中均表达,因此Pick1敲除小鼠的不育可能是由于神经内分泌功能受损或精子发生异常所致。为了区分这两种可能性,我们通过生精小管显微注射含有 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,我们发现睾丸中PICK1的表达挽救了Pick1敲除小鼠的生精异常和男性不育症。我们的结果表明,不孕症是由睾丸而不是其他器官缺乏PICK1引起的。此外,我们发现生精小管显微注射慢病毒对于产生睾丸特异性转基因小鼠有很强的偏好。
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.
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