Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice
Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice
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DOI：
10.1093/emboj/21.11.2591
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发表时间：
2002-06-03
期刊：
影响因子：
11.4
通讯作者：
Mezger, V
中科院分区：
文献类型：
--
作者：
Kallio, M;Chang, YH;Mezger, V
热休克因子2是四种脊椎动物HSF之一，是热休克基因表达的转录调节因子，在胚胎发生和精子发生过程中活跃，其功能和靶点未知。通过破坏Hsf2基因，我们发现，虽然HSF2的缺乏不会导致胚胎死亡，但Hsf2(-/-)小鼠的两性都会出现大脑异常、减数分裂和配子发生缺陷。大脑紊乱的特征是侧脑室和第三脑室扩大以及海马和纹状体减少，这与成人神经上皮增殖细胞和一些室管膜细胞中的 HSF2 表达相关。在Hsf2(-/-)雄性中，许多发育中的精母细胞通过细胞凋亡以特定阶段的方式被消除，并且粗线期精母细胞在同源染色体之间的联会复合体中也表现出结构缺陷。 Hsf2(-/-)雌性患有多种生育缺陷：异常卵子的产生、卵泡数量减少以及出血性囊性卵泡的存在与减数分裂缺陷一致。 Hsf2(-/-) 雌性还表现出激素反应缺陷，可以通过超排卵治疗来挽救，并且表现出黄体生成素受体 mRNA 的异常率。
Heat shock factor 2, one of the four vertebrate HSFs, transcriptional regulators of heat shock gene expression, is active during embryogenesis and spermatogenesis, with unknown functions and targets. By disrupting the Hsf2 gene, we show that, although the lack of HSF2 is not embryonic lethal, Hsf2(-/-) mice suffer from brain abnormalities, and meiotic and gameto genesis defects in both genders. The disturbances in brain are characterized by the enlargement of lateral and third ventricles and the reduction of hippocampus and striatum, in correlation with HSF2 expression in proliferative cells of the neuroepithelium and in some ependymal cells in adults. Many developing spermatocytes are eliminated via apoptosis in a stage-specific manner in Hsf2(-/-) males, and pachytene spermatocytes also display structural defects in the synaptonemal complexes between homologous chromosomes. Hsf2(-/-) females suffer from multiple fertility defects: the production of abnormal eggs, the reduction in ovarian follicle number and the presence of hemorrhagic cystic follicles are consistent with meiotic defects. Hsf2(-/-) females also display hormone response defects, that can be rescued by superovulation treatment, and exhibit abnormal rates of luteinizing hormone receptor mRNAs.