Nishimura Darryl Y, Fath Melissa, Mullins Robert F, Searby Charles, Andrews Michael, Davis Roger, Andorf Jeaneen L, Mykytyn Kirk, Swiderski Ruth E, Yang Baoli, Carmi Rivka, Stone Edwin M, Sheffield Val C
Department of Pediatrics, Division of Medical Genetics, University of Iowa, Iowa City, IA 52242, USA.
Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16588-93. doi: 10.1073/pnas.0405496101. Epub 2004 Nov 11.
Bardet-Biedl syndrome (BBS) is a heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, hypogenitalism, and an increased incidence of diabetes and hypertension. No information is available regarding the specific function of BBS2. We show that mice lacking Bbs2 gene expression have major components of the human phenotype, including obesity and retinopathy. In addition, these mice have phenotypes associated with cilia dysfunction, including retinopathy, renal cysts, male infertility, and a deficit in olfaction. With the exception of male infertility, these phenotypes are not caused by a complete absence of cilia. We demonstrate that BBS2 retinopathy involves normal retina development followed by apoptotic death of photoreceptors, the primary ciliated cells of the retina. Photoreceptor cell death is preceded by mislocalization of rhodopsin, indicating a defect in transport. We also demonstrate that Bbs2(-/-) mice and a second BBS mouse model, Bbs4(-/-), have a defect in social function. The evaluation of Bbs2(-/-) mice indicates additional phenotypes that should be evaluated in human patients, including deficits in social interaction and infertility.
巴德-比埃尔综合征（BBS）是一种具有异质性、多效性的人类疾病，其特征为肥胖、视网膜病变、多指（趾）畸形、肾脏和心脏畸形、学习障碍、生殖器发育不全以及糖尿病和高血压发病率增加。目前尚无关于BBS2具体功能的信息。我们发现，缺乏Bbs2基因表达的小鼠具有人类疾病的主要特征，包括肥胖和视网膜病变。此外，这些小鼠还具有与纤毛功能障碍相关的特征，包括视网膜病变、肾囊肿、男性不育以及嗅觉缺陷。除男性不育外，这些特征并非由纤毛完全缺失所致。我们证明，BBS2视网膜病变包括正常的视网膜发育，随后是光感受器（视网膜的主要纤毛细胞）的凋亡死亡。光感受器细胞死亡之前，视紫红质会发生错误定位，表明存在转运缺陷。我们还证明，Bbs2（-/-）小鼠和另一种BBS小鼠模型Bbs4（-/-）存在社交功能缺陷。对Bbs2（-/-）小鼠的评估表明，人类患者中也应评估其他特征，包括社交互动缺陷和不育。
