Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice
Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice
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DOI：
10.1038/ng1168
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发表时间：
2003-06-01
期刊：
影响因子：
30.8
通讯作者：
Chalepakis, G
中科院分区：
文献类型：
--
作者：
Vrontou, S;Petrou, P;Chalepakis, G
表皮和真皮之间紧密联系的丧失是几种水泡性疾病的基础，并且通常是由细胞外基质（ECM）蛋白功能受损引起的（1，2）。在这里，我们描述了一种新的蛋白质在小鼠，Fras 1，这是专门检测到的一个线性的方式下的表皮和其他上皮细胞在胚胎的基底面。Fras 1功能的丧失导致小鼠胚胎发育过程中表皮下出血性水泡的形成以及单侧或双侧肾发育不全。出生后，纯合子Fras 1突变体有眼睑和手指融合和单侧肾发育不全或发育不良。在Fras 1（-/-）小鼠中观察到的缺陷与现有的bl（起泡）小鼠突变体的缺陷表型相似（3，4），其被认为是人类遗传疾病Fraser综合征的模型（5，6）。我们发现bl/bl纯合子胚胎缺乏Fras 1蛋白，这与Fras 1在这些小鼠中突变的发现一致（6）。总之，我们的数据表明，扰动的细胞外空间的组成下上皮细胞可以解释在小鼠和弗雷泽综合征表现的水泡表型在人类的发病。
Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins(1,2). Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1(-/-) mice phenocopy those of the existing bl (blebbed) mouse mutants(3,4), which have been considered a model for the human genetic disorder Fraser syndrome(5,6). We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice(6). In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.