Meiotic Sex Chromosome Inactivation Is Disrupted in Sterile Hybrid Male House Mice
Meiotic Sex Chromosome Inactivation Is Disrupted in Sterile Hybrid Male House Mice
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DOI：
10.1534/genetics.112.148635
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发表时间：
2013-03-01
期刊：
影响因子：
3.3
通讯作者：
Nachman, Michael W.
中科院分区：
文献类型：
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作者：
Campbell, Polly;Good, Jeffrey M.;Nachman, Michael W.
在雄性哺乳动物中，X和Y染色体在初级精母细胞中被减数分裂性染色体失活(MSCI)转录沉默，并在精子发生期间保持抑制。在这里，我们测试了一个长期存在的假设，即扰乱MSCI可能有助于异性恋杂交男性的优先不育。我们研究了野生近交系小鼠和家鼠的杂交，其中不育是不对称的：具有肌肉小鼠母亲的F-1雄性是不育的或接近不育的，而母亲是小家鼠的F-1雄性是正常的。在之前的工作中，我们发现在不育但没有生育能力的F-1雄鼠的睾丸中普遍存在X连锁基因的过度表达。在这里，我们问，这种过度表达是否明确地说是摩根士丹利资本国际(MSCI)被扰乱的结果。为了做到这一点，我们从精子发生的不同阶段分离细胞，并使用定量聚合酶链式反应检测几个基因的表达。我们发现，在不育的F-1初级精母细胞中，X的过度表达与MSCI的发生是一致的，并持续存在于减数分裂后的精子细胞中。然后，我们利用一系列重组的X基因类型，询问杂交种中X的过度表达是否受X染色体上的顺式作用基因座控制。我们发现事实并非如此。相反，肌肉分枝杆菌X染色体近端的一个大间隔与杂交种的过度表达和不孕症表型的严重程度有关。这些结果表明，X连锁杂交种雄性不育与MSCI的干扰有很强的相关性，并表明X染色体上的转录调控基因在精子发生过程中是重要的。
In male mammals, the X and Y chromosomes are transcriptionally silenced in primary spermatocytes by meiotic sex chromosome inactivation (MSCI) and remain repressed for the duration of spermatogenesis. Here, we test the longstanding hypothesis that disrupted MSCI might contribute to the preferential sterility of heterogametic hybrid males. We studied a cross between wild-derived inbred strains of Mus musculus musculus and M. m. domesticus in which sterility is asymmetric: F-1 males with a M. m. musculus mother are sterile or nearly so while F-1 males with a M. m. domesticus mother are normal. In previous work, we discovered widespread overexpression of X-linked genes in the testes of sterile but not fertile F-1 males. Here, we ask whether this overexpression is specifically a result of disrupted MSCI. To do this, we isolated cells from different stages of spermatogenesis and measured the expression of several genes using quantitative PCR. We found that X overexpression in sterile F-1 primary spermatocytes is coincident with the onset of MSCI and persists in postmeiotic spermatids. Using a series of recombinant X genotypes, we then asked whether X overexpression in hybrids is controlled by cis-acting loci across the X chromosome. We found that it is not. Instead, one large interval in the proximal portion of the M. m. musculus X chromosome is associated with both overexpression and the severity of sterility phenotypes in hybrids. These results demonstrate a strong association between X-linked hybrid male sterility and disruption of MSCI and suggest that transacting loci on the X are important for the transcriptional regulation of the X chromosome during spermatogenesis.