Thymus, kidney and craniofacial abnormalities in Six1 deficient mice
Thymus, kidney and craniofacial abnormalities in Six1 deficient mice
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DOI：
10.1016/s0925-4773(03)00065-0
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发表时间：
2003-06-01
影响因子：
2.6
通讯作者：
Maire, P
中科院分区：
文献类型：
--
作者：
Laclef, C;Souil, E;Maire, P
基因在脊椎动物胚胎发育过程中广泛表达，提示它们与不同的分化过程有关。为了确定SIX1基因的功能，我们构建了SIX1缺陷小鼠，方法是用β-半乳糖苷酶基因替换SIX1基因的第一个外显子。我们之前已经证明，缺乏六个]的小鼠出生时就会死于胸骨缺陷和严重的肌肉发育不全，影响到身体的大部分肌肉。在这里，我们报告SIX1(-/-)新生儿也缺乏肾脏和胸腺，并表现出强烈的头面部结构紊乱，即内耳、鼻腔、头面部骨骼以及泪腺和腮腺。在胚胎发育的不同阶段，X-Gal染色显示，这些器官缺陷可能与胚胎原基结构中六种基因的表达有关。因此，SIX1(-/-)小鼠的胎儿异常似乎是由于在器官发生的早期阶段缺乏SIX1同源蛋白所致。有趣的是，这六个I缺陷与Eya1突变引起的表型非常相似，Eya1突变是人类Bor综合征的原因。对SIX1和Eya1缺陷小鼠的密切比较有力地表明了这两个因素之间的功能联系。Pax基因突变也会导致类似的表型，这表明哺乳动物的几种器官发生都需要一个包括Pax、Six和Eya基因在内的调控网络。(C)2003爱思唯尔爱尔兰科学有限公司。保留所有权利。
genes are widely expressed during vertebrate embryogenesis, suggesting that they are implicated in diverse differentiation processes. To determine the functions of the Six] gene, we constructed Six1-deficient mice by replacing its first exon by the beta-galactosidase gene. We have previously shown that mice lacking Six] die at birth due to thoracic skeletal defects and severe muscle hypoplasia affecting most of the body muscles. Here, we report that Six1(-/-) neonates also lack a kidney and thymus, as well as displaying a strong disorganisation of craniofacial structures, namely the inner ear, the nasal cavity, the craniofacial skeleton, and the lacrimal and parotid glands. These organ defects can be correlated with Six] expression in the embryonic primordium structures as revealed by X-Gal staining at different stages of embryogenesis. Thus, the fetal abnormalities of Six1(-/-) mice appear to result from the absence of the Six1 homeoprotein during early stages of organogenesis. Interestingly, these Six I defects are very similar to phenotypes caused by mutations of Eya1, which are responsible for the BOR syndrome in humans. Close comparison of Six1 and Eya1 deficient mice strongly suggests a functional link between these two factors. Pax gene mutations also lead to comparable phenotypes, suggesting that a regulatory network including the Pax, Six and Eya genes is required for several types of organogenesis, in mammals. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.