The Y-Encoded Gene Zfy2 Acts to Remove Cells with Unpaired Chromosomes at the First Meiotic Metaphase in Male Mice

The Y-Encoded Gene Zfy2 Acts to Remove Cells with Unpaired Chromosomes at the First Meiotic Metaphase in Male Mice
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DOI:
10.1016/j.cub.2011.03.057
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发表时间:
2011-05-10
期刊:
影响因子:
9.2
通讯作者:
Burgoyne, Paul S.
Burgoyne, Paul S.
中科院分区:
生物学1区
文献类型:
--
作者:
Vernet, Nadege;Mahadevaiah, Shantha K.;Burgoyne, Paul S.

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在雄性而非雌性哺乳动物减数分裂期间,在第一次减数分裂中期(MI)具有未配对(单价)染色体的细胞存在有效的凋亡消除[1]。在XSxr(a)O雄性小鼠[2]的单价X染色体反应中观察到MI精母细胞的凋亡消除,其中X染色体携带Sxr(a)[3,4],Y染色体衍生的性逆转因子,包括睾丸决定簇Sry。Sxr(B)是Sxr(a)衍生的变体,其中缺失去除了6个Y短臂基因,并产生了跨越缺失断裂点的Zfy 2/Zfy 1融合基因[4,5]。XSxr(B)O雄性具有精原细胞停滞,可以通过从缺失中重新添加Eif 2s 3 y作为转基因来克服;然而,XSxr(B)OEif 2s 3 y转基因雄性未显示出对单价的响应的MI精母细胞的预期消除[6]。在这里,我们表明,这些XSxr(B)OEif 2s 3 y男性有一个受损的细胞凋亡反应与完成第一次减数分裂,但没有第二次减数分裂。然后,我们表明,Zfy 2(但不是密切相关的Zfy 1)是足以恢复细胞凋亡的X单价的反应。这些发现提供了进一步的见解的基础上,低得多的传播染色体错误起源于第一次减数分裂的男性比女性[7]。
During male but not female mammalian meiosis, there is efficient apoptotic elimination of cells with unpaired (univalent) chromosomes at the first meiotic metaphase (MI) [1]. Apoptotic elimination of MI spermatocytes is seen in response to the univalent X chromosome of XSxr(a)O male mice [2], in which the X chromosome carries Sxr(a) [3, 4], the Y-chromosome-derived sex-reversal factor that includes the testis determinant Sry. Sxr(b) is an Sxr(a)-derived variant in which a deletion has removed six Y short-arm genes and created a Zfy2/Zfy1 fusion gene spanning the deletion breakpoint [4, 5]. XSxr(b)O males have spermatogonial arrest that can be overcome by the re-addition of Eif2s3y from the deletion as a transgene; however, XSxr(b)OEif2s3y transgenic males do not show the expected elimination of MI spermatocytes in response to the univalent [6]. Here we show that these XSxr(b)OEif2s3y males have an impaired apoptotic response with completion of the first meiotic division, but there is no second meiotic division. We then show that Zfy2 (but not the closely related Zfy1) is sufficient to reinstate the apoptotic response to the X univalent. These findings provide further insight into the basis for the much lower transmission of chromosomal errors originating at the first meiotic division in men than in women [7].