Electroporated transgene-rescued spermatogenesis in infertile mutant mice with a Sertoli cell defect
Electroporated transgene-rescued spermatogenesis in infertile mutant mice with a Sertoli cell defect
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DOI：
10.1095/biolreprod.101.001743
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发表时间：
2002-09-01
影响因子：
3.6
通讯作者：
Nishimune, Y
中科院分区：
文献类型：
--
作者：
Yomogida, K;Yagura, Y;Nishimune, Y
由于缺乏有用的研究系统，大多数人类男性不育的分子基础由于精子发生障碍而知之甚少。为了研究支持支持细胞在哺乳动物精子发生中的作用，我们改进了体内生精小管的电穿孔技术。由于支持细胞在成熟的睾丸中几乎不会增殖，线性转基因不会整合到基因组中，因此会迅速降解。然而，环状表达载体在Sertoli细胞中能长期稳定表达。通过电转化完整的cDNA，我们挽救了不育小鼠Sl(17H)/Sl(17H)突变小鼠的精子发生缺陷，这些突变小鼠的支持细胞中干细胞因子部分功能障碍。这种基因转移系统的应用将有助于理解精子发生和开发新的男性不育基因治疗方法。
The molecular basis of most human male infertility arising from spermatogenesis disruption is poorly understood because of a lack of useful investigation systems. To study the roles of the supporting Sertoli cells in mammalian spermatogenesis, we improved an electroporation technique for seminiferous tubules in vivo. Because Sertoli cells barely proliferate in mature testis, linear transgenes are not incorporated into the genome and quickly degrade. However, circular expression vector is stably expressed in Sertoli cells for a long period. By electrotransformation of a complete cDNA, we rescued defective spermatogenesis in infertile Sl(17H)/Sl(17H) mutant mice with partial dysfunction of stem cell factor in Sertoli cells. Application of this gene transfer system will facilitate both the understanding of spermatogenesis and the development of new gene therapies for human male infertility.