A Mouse Model for Meckel Syndrome Type 3
A Mouse Model for Meckel Syndrome Type 3
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DOI：
10.1681/asn.2008040412
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发表时间：
2009-04-01
影响因子：
13.6
通讯作者：
Davisson, Muriel T.
中科院分区：
文献类型：
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作者：
Cook, Susan A.;Collin, Gayle B.;Davisson, Muriel T.
Meckel-Gruber综合征3型（MKS3; OMIM 607361）是一种以双侧多囊肾病为特征的严重常染色体隐性遗传病。与MKS3相关的其他畸形包括肝脏囊性改变、多指畸形和脑部异常（枕脑膨出、脑积水和Dandy walker型小脑异常）。这种疾病被认为是由初级纤毛缺陷引起的。在人类中，潜在的突变基因TMEM67编码跨膜蛋白67，也称为麦kelin (OMIM 609884)，这是肾上皮细胞和初级纤毛膜的一个完整蛋白。在这里，我们描述了小鼠同源基因Tmem67的自发缺失，导致多囊肾病和出生后3周死亡。脑积水也发生在一些突变体中。我们通过转基因拯救验证了突变基因，并通过显微计算机断层扫描、组织学、扫描电镜和免疫组织化学表征了突变基因的表型。该突变体为MKS3提供了小鼠模型，并为研究初级纤毛在肾功能中的作用提供了越来越多的哺乳动物模型。
Meckel-Gruber syndrome type 3 (MKS3; OMIM 607361) is a severe autosomal recessive disorder characterized by bilateral polycystic kidney disease. Other malformations associated with MKS3 include cystic changes in the liver, polydactyly, and brain abnormalities (occipital encephalocele, hydrocephalus, and Dandy Walker-type cerebellar anomalies). The disorder is hypothesized to be caused by defects in primary cilia. In humans, the underlying mutated gene, TMEM67, encodes transmembrane protein 67, also called meckelin (OMIM 609884), which is an integral protein of the renal epithelial cell and membrane of the primary cilium. Here, we describe a spontaneous deletion of the mouse ortholog, Tmem67, which results in polycystic kidney disease and death by 3 wk after birth. Hydrocephalus also occurs in some mutants. We verified the mutated gene by transgenic rescue and characterized the phenotype with microcomputed tomography, histology, scanning electron microscopy, and immunohistochemistry. This mutant provides a mouse model for MKS3 and adds to the growing set of mammalian models essential for studying the role of the primary cilium in kidney function.