A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2.

A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2.
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转录因子LMO4在胸腺发育中的一种新作用,通过与CID2的遗传相互作用2。

DOI:
10.1002/dvdy.22334
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发表时间:
2010-07
影响因子:
2.5
通讯作者:
Bamforth, Simon D.
Bamforth, Simon D.
中科院分区:
生物学3区
文献类型:
--
作者:
Michell, Anna C.;Braganca, Jose;Broadbent, Carol;Joyce, Bradley;Franklyn, Angela;Schneider, Juergen E.;Bhattacharya, Shoumo;Bamforth, Simon D.

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转录调节因子Cited 2在小鼠中的缺失导致胚胎死亡、心血管畸形、肾上腺发育不全、颅神经节融合、露脑畸形和左右图案缺陷,所有这些都表现为不同程度的异常。在不同遗传背景下观察到的表型异质性表明存在遗传和环境修饰因子。缺乏含LIM结构域的蛋白Lmo 4的小鼠与Cited 2无效胚胎共享特定表型,如胚胎致死、颅神经节融合和露脑畸形。这些共有的表型表明Lmo 4可能是Cited 2表型的潜在遗传修饰剂。Lmo 4缺陷胚胎的检查显示部分渗透性心血管畸形和胸腺发育不全。对Lmo 4; Cited 2复合突变体的检测表明,Cited 2和Lmo 4在控制胸腺发育方面存在遗传互作。我们的数据表明,这可能发生,在一定程度上,通过控制一个共同的靶基因,Tbx 1,这是必要的正常胸腺发育的表达。发展动力学239:1988-1994,2010年。© 2010 Wiley-Liss公司。
Deletion of the transcriptional modulator Cited2 in the mouse results in embryonic lethality, cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left–right patterning defects, all seen with a varying degree of penetrance. The phenotypic heterogeneity, observed on different genetic backgrounds, indicates the existence of both genetic and environmental modifiers. Mice lacking the LIM domain-containing protein Lmo4 share specific phenotypes with Cited2 null embryos, such as embryonic lethality, cranial ganglia fusion, and exencephaly. These shared phenotypes suggested that Lmo4 may be a potential genetic modifier of the Cited2 phenotype. Examination of Lmo4-deficient embryos revealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination of Lmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 in control of thymus development. Our data suggest that this may occur, in part, through control of expression of a common target gene, Tbx1, which is necessary for normal thymus development. Developmental Dynamics 239:1988–1994, 2010. © 2010 Wiley-Liss, Inc.
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