A missense mutation in the transcription factor ETV5 leads to sterility, increased embryonic and perinatal death, postnatal growth restriction, renal asymmetry and polydactyly in the mouse.
A missense mutation in the transcription factor ETV5 leads to sterility, increased embryonic and perinatal death, postnatal growth restriction, renal asymmetry and polydactyly in the mouse.
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DOI：
10.1371/journal.pone.0077311
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
O'Bryan MK
中科院分区：
文献类型：
--
作者：
Jamsai D;Clark BJ;Smith SJ;Whittle B;Goodnow CC;Ormandy CJ;O'Bryan MK
ETV5（Ets variant gene 5）是一种转录因子，是生育所必需的。在这项研究中，我们证明了ETV5在小鼠的胚胎和出生后发育过程中起着额外的作用。通过全基因组小鼠诱变方法，我们产生了在Etv5基因的外显子12中携带无义突变的不育小鼠品系。该突变导致位置412处的赖氨酸转化为蛋白质的ETS DNA结合结构域内的提前终止密码子（PTC）。我们发现，含有PTC的等位基因产生了一种高度不稳定的mRNA，这反过来又导致了检测不到ETV5蛋白的水平。Etv5突变导致雄性和雌性不育，如通过育种实验所确定的。突变体雄性由于精原细胞的进行性损失而不育，这最终导致8周龄时仅支持细胞表型。此外，ETV 5靶基因Cxcr4和Ccl9在突变的新生儿睾丸中显著下调。CXCR4和CCL9分别与精原细胞的维持和迁移有关。此外，Etv5突变导致几种发育异常，包括胚胎和围产期死亡率增加，出生后生长受限，多指（趾）畸形和肾不对称。因此，我们的数据定义了ETV 5在发育的许多方面的生理作用，包括胚胎和围产期存活、出生后生长、肢体发育、肾脏发育和生育力。
ETV5 (Ets variant gene 5) is a transcription factor that is required for fertility. In this study, we demonstrate that ETV5 plays additional roles in embryonic and postnatal developmental processes in the mouse. Through a genome-wide mouse mutagenesis approach, we generated a sterile mouse line that carried a nonsense mutation in exon 12 of the Etv5 gene. The mutation led to the conversion of lysine at position 412 into a premature termination codon (PTC) within the ETS DNA binding domain of the protein. We showed that the PTC-containing allele produced a highly unstable mRNA, which in turn resulted in an undetectable level of ETV5 protein. The Etv5 mutation resulted in male and female sterility as determined by breeding experiments. Mutant males were sterile due to a progressive loss of spermatogonia, which ultimately resulted in a Sertoli cell only phenotype by 8 week-of-age. Further, the ETV5 target genes Cxcr4 and Ccl9 were significantly down-regulated in mutant neonate testes. CXCR4 and CCL9 have been implicated in the maintenance and migration of spermatogonia, respectively. Moreover, the Etv5 mutation resulted in several developmental abnormalities including an increased incidence of embryonic and perinatal lethality, postnatal growth restriction, polydactyly and renal asymmetry. Thus, our data define a physiological role for ETV5 in many aspects of development including embryonic and perinatal survival, postnatal growth, limb patterning, kidney development and fertility.
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影响因子：
3.7
作者：
Jamsai D;O'Connor AE;Deboer KD;Clark BJ;Smith SJ;Browne CM;Bensley JG;Merriman JA;Yuen WS;Koopman P;Jones KT;O'Bryan MK
通讯作者：
O'Bryan MK
影响因子：
6.7
作者：
O'Bryan, Moira K.;Grealy, Alicia;Jamsai, Duangporn
通讯作者：
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影响因子：
6.1
作者：
McLachlan, R. I.;Rajpert-De Meyts, E.;Skakkebaek, N. E.
通讯作者：
Skakkebaek, N. E.
影响因子：
2.7
作者：
Paratore, C;Brugnoli, G;Sommer, L
通讯作者：
Sommer, L
影响因子：
4
作者：
Eo, Jinwon;Shin, Hyejin;Lim, Jade Hyunjung
通讯作者：
Lim, Jade Hyunjung