Dix D J, Allen J W, Collins B W, Mori C, Nakamura N, Poorman-Allen P, Goulding E H, Eddy E M
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3264-8. doi: 10.1073/pnas.93.8.3264.
In addition to the five 70-kDa heat shock proteins (HSP70) common to germ cells and somatic tissues of mammals, spermatogenic cells synthesize HSP70-2 during meiosis. To determine if this unique stress protein has a critical role in meiosis, we used gene-targeting techniques to disrupt Hsp70-2 in mice. Male mice homozygous for the mutant allele (Hsp70-2 -/-) did not synthesize HSP70-2, lacked postmeiotic spermatids and mature sperm, and were infertile. However, neither meiosis nor fertility was affected in female Hsp70-2 -/- mice. We previously found that HSP70-2 is associated with synaptonemal complexes in the nucleus of meiotic spermatocytes from mice and hamsters. While synaptonemal complexes assembled in Hsp70-2 -/- spermatocytes, structural abnormalities became apparent in these cells by late prophase, and development rarely progressed to the meiotic divisions. Furthermore, analysis of nuclei and genomic DNA indicated that the failure of meiosis in Hsp70-2 -/- mice was coincident with a dramatic increase in spermatocyte apoptosis. These results suggest that HSP70-2 participates in synaptonemal complex function during meiosis in male germ cells and is linked to mechanisms that inhibit apoptosis.
除了哺乳动物生殖细胞和体细胞共有的5种70-kDa热休克蛋白（HSP70）外，生精细胞在减数分裂期间还合成HSP70-2。为了确定这种独特的应激蛋白在减数分裂中是否具有关键作用，我们使用基因靶向技术在小鼠中破坏Hsp70-2。突变等位基因（Hsp70-2 -/-）纯合的雄性小鼠不合成HSP70-2，缺乏减数分裂后的精子细胞和成熟精子，并且不育。然而，雌性Hsp70-2 -/-小鼠的减数分裂和生育能力均未受到影响。我们之前发现HSP70-2与小鼠和仓鼠减数分裂精子细胞细胞核中的联会复合体相关。虽然联会复合体在Hsp70-2 -/-精子细胞中组装，但在前期晚期这些细胞中出现明显的结构异常，并且发育很少进展到减数分裂期。此外，对细胞核和基因组DNA的分析表明，Hsp70-2 -/-小鼠减数分裂失败与精子细胞凋亡的显著增加同时发生。这些结果表明，HSP70-2在雄性生殖细胞减数分裂期间参与联会复合体功能，并与抑制细胞凋亡的机制有关。
