Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly
Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly
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DOI：
10.1073/pnas.0402354101
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发表时间：
2004-06-08
影响因子：
11.1
通讯作者：
Sheffield, VC
中科院分区：
文献类型：
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作者：
Mykytyn, K;Mullins, RF;Sheffield, VC
由Bardet-Biedl综合征（BBS）基因编码的蛋白质的功能尚不清楚。这些基因中的突变导致多效人类疾病BBS，其特征在于肥胖、视网膜病、多指（趾）畸形、肾和心脏畸形、学习障碍和生殖器发育不良。次要特征包括糖尿病和高血压。最近，有人提出BBS表型是纤毛形成或功能缺乏的结果。在这项研究中，我们发现缺乏Bbs 4蛋白的小鼠具有人类表型的主要组成部分，包括肥胖和视网膜变性。我们发现，Bbs 4-null小鼠发展运动和初级纤毛，表明Bbs 4是不需要全球纤毛形成。有趣的是，雄性Bbs 4基因缺失小鼠不形成精子鞭毛，并且Bbs 4视网膜病变涉及光感受器（视网膜的初级纤毛细胞）的凋亡性死亡。这些突变数据表明BBS蛋白的功能和纤毛之间的联系。为了进一步评估纤毛和BIBS之间的关联，我们在模式生物中进行了BBS蛋白的同源性比较，发现BBS蛋白在纤毛生物中特别保守。
The functions of the proteins encoded by the Bardet-Biedl syndrome (BBS) genes are unknown. Mutations in these genes lead to the pleiotropic human disorder BBS, which is characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Secondary features include diabetes mellitus and hypertension. Recently, it has been suggested that the BBS phenotypes are the result of a lack of cilia formation or function. In this study, we show that mice lacking the Bbs4 protein have major components of the human phenotype, including obesity and retinal degeneration. We show that Bbs4-null mice develop both motile and primary cilia, demonstrating that Bbs4 is not required for global cilia formation. Interestingly, male Bbs4-null mice do not form spermatozoa flagella, and BBS4 retinopathy involves apoptotic death of photoreceptors, the primary ciliated cells of the retina. These mutation data demonstrate a connection between the function of a BBS protein and cilia. To further evaluate an association between cilia and BIBS, we performed homology comparisons of BBS proteins in model organisms and find that BBS proteins are specifically conserved in ciliated organisms.