Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis.
Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis.
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DOI：
10.1371/journal.pone.0131066
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Strathdee D
中科院分区：
文献类型：
--
作者：
Cadalbert LC;Ghaffar FN;Stevenson D;Bryson S;Vaz FM;Gottlieb E;Strathdee D
Barth综合征是一种X连锁线粒体疾病，其症状包括中性粒细胞减少症和心肌病。这些症状是疾病最显著的临床后果，越来越多的人认识到疾病具有可变的表现。Xq28中Taz基因的突变被认为是通过改变线粒体脂质含量和线粒体功能而导致这种情况的原因。在X染色体上携带Taz靶向突变的雄性嵌合体是不育的。Taz基因敲除嵌合体的睾丸比对照组小，这与精母细胞减数分裂到精子发生的进程中断有关。Taz基因敲除的ES细胞在体外分化为生殖细胞时也表现出缺陷。突变精母细胞未能进展过去粗线期阶段的减数分裂，并有较高水平的DNA双链损伤和内源性反转录转座子活性水平的增加。总之，这些数据揭示了Taz在帮助维持减数分裂中基因组完整性和促进生殖细胞分化方面的新作用。我们已经揭示了Taz蛋白的一种新功能，这应该有助于了解Taz基因的破坏如何导致巴斯综合症的复杂症状。
Barth syndrome is an X-linked mitochondrial disease, symptoms of which include neutropenia and cardiac myopathy. These symptoms are the most significant clinical consequences of a disease, which is increasingly recognised to have a variable presentation. Mutation in the Taz gene in Xq28 is thought to be responsible for the condition, by altering mitochondrial lipid content and mitochondrial function. Male chimeras carrying a targeted mutation of Taz on their X-chromosome were infertile. Testes from the Taz knockout chimeras were smaller than their control counterparts and this was associated with a disruption of the progression of spermatocytes through meiosis to spermiogenesis. Taz knockout ES cells also showed a defect when differentiated to germ cells in vitro. Mutant spermatocytes failed to progress past the pachytene stage of meiosis and had higher levels of DNA double strand damage and increased levels of endogenous retrotransposon activity. Altogether these data revealed a novel role for Taz in helping to maintain genome integrity in meiosis and facilitating germ cell differentiation. We have unravelled a novel function for the Taz protein, which should contribute to an understanding of how a disruption of the Taz gene results in the complex symptoms underlying Barth Syndrome.
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影响因子：
46.9
作者：
Jackson, AL;Bartz, SR;Linsley, PS
通讯作者：
Linsley, PS
影响因子：
3.7
作者：
Clarke SL;Bowron A;Gonzalez IL;Groves SJ;Newbury-Ecob R;Clayton N;Martin RP;Tsai-Goodman B;Garratt V;Ashworth M;Bowen VM;McCurdy KR;Damin MK;Spencer CT;Toth MJ;Kelley RI;Steward CG
通讯作者：
Steward CG
影响因子：
2
作者：
Gonzalez, IL
通讯作者：
Gonzalez, IL
影响因子：
4.8
作者：
Acehan, Devrim;Vaz, Frederic;Khuchua, Zaza
通讯作者：
Khuchua, Zaza
影响因子：
30.8
作者：
Bione, S;DAdamo, P;Toniolo, D
通讯作者：
Toniolo, D