PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice.
PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice.
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DOI：
10.15252/emmm.201708515
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发表时间：
2018-05
影响因子：
11.1
通讯作者：
Arnoult C
中科院分区：
文献类型：
--
作者：
Christou-Kent M;Kherraf ZE;Amiri-Yekta A;Le Blévec E;Karaouzène T;Conne B;Escoffier J;Assou S;Guttin A;Lambert E;Martinez G;Boguenet M;Fourati Ben Mustapha S;Cedrin Durnerin I;Halouani L;Marrakchi O;Makni M;Latrous H;Kharouf M;Coutton C;Thierry-Mieg N;Nef S;Bottari SP;Zouari R;Issartel JP;Ray PF;Arnoult C
卵母细胞减数分裂缺陷症（OMD）是一种以产生未成熟卵母细胞为特征的原发性不育症，其遗传原因在很大程度上仍未被探索。使用全外显子组测序，我们发现23名OMD受试者中有26%在PATL 2中携带相同的纯合无义致病突变，PATL 2是一种编码推定RNA结合蛋白的基因。使用Patl 2基因敲除小鼠，我们证实了PATL 2缺陷干扰卵母细胞成熟，因为卵母细胞和受精卵分别表现出形态和发育缺陷。PATL 2的两栖动物同源基因作为CPEB的伴侣参与卵母细胞mRNA的调节。然而，Patl 2在小鼠卵母细胞发育过程中的表达谱，以及Cpeb 1，Msy 2和Ddx 6（三种卵母细胞RNA调节剂）的共定位实验表明Patl 2在哺乳动物中的原始作用。因此，WT和Patl 2 −/−动物卵母细胞的转录组学分析表明，在Patl 2缺失的情况下，参与卵母细胞成熟和早期胚胎发育的选定数量的高度相关基因的表达水平被失调。总之，PATL 2是哺乳动物卵母细胞成熟的一个新的作用因子，其失效导致人类OMD。
The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA‐binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects, respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA regulators) suggest an original role for Patl2 in mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2 −/− animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.
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DOI：
10.1530/rep-15-0107
发表时间：
2015-06
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Alam SM;Konno T;Soares MJ
通讯作者：
Soares MJ
影响因子：
11.4
作者：
Braun, Joerg E.;Tritschler, Felix;Haas, Gabrielle;Igreja, Catia;Truffault, Vincent;Weichenrieder, Oliver;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa
影响因子：
2.5
作者：
Fujii, Haruko;Tatsumi, Keiji;Fujii, Shingo
通讯作者：
Fujii, Shingo
DOI：
10.1073/pnas.1423533112
发表时间：
2015-05-05
影响因子：
11.1
作者：
Huang, Ya-Lin;Anvarian, Zeinab;Niehrs, Christof
通讯作者：
Niehrs, Christof
PATL2 的双等位基因突变导致女性不孕，其特征是卵母细胞成熟停滞
影响因子：
9.8
作者：
Chen, Biaobang;Zhang, Zhihua;Wang, Lei
通讯作者：
Wang, Lei