Mokrzan Elaine M, Lewis Jacqueline S, Mykytyn Kirk
Department of Pharmacology, Division of Human Genetics, Ohio State University, Columbus, Ohio 43210, USA.
Nephron Exp Nephrol. 2007;106(3):e88-96. doi: 10.1159/000103021. Epub 2007 May 22.
Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder that comprises numerous features, including renal cystic disease. Twelve BBS genes have been identified (BBS1-12). Although the exact functions of the BBS proteins are unknown, evidence suggests that they are involved in cilia assembly, maintenance and/or function. Renal primary cilia dysfunction can lead to cystic kidney disease. To test whether lacking Bbs4 affects cilia assembly and structure, we analyzed primary cilia in Bbs4-null (Bbs4(-/-)) mice.
Renal tubule cultures from wild-type (Bbs4(+/+)) and Bbs4(-/-) mice were examined by immunocytochemistry and scanning and transmission electron microscopy.
Our culture conditions generated ciliated epithelial cells that were mostly of collecting duct origin. The microtubule ultrastructure of cilia and basal bodies did not appear disrupted in Bbs4(-/-) cells. In control cells, cilia length was maximal at 7 days in culture. In cells cultured from Bbs4(-/-) mice, cilia were shorter initially, but surpassed the length of control cilia by 10 days. Renal primary cilia were also longer in Bbs4(-/-) kidneys.
Lacking Bbs4 does not lead to aberrant cilia or basal body structure. However, the dynamics of cilia assembly is altered in Bbs4(-/-) cells, suggesting a role for Bbs4 in the regulation of ciliary assembly.
巴德-比埃尔综合征（BBS）是一种具有多种特征的遗传性疾病，包括肾囊性疾病。已鉴定出12个BBS基因（BBS1 - 12）。尽管BBS蛋白的确切功能尚不清楚，但有证据表明它们参与纤毛的组装、维持和/或功能。肾初级纤毛功能障碍可导致多囊肾病。为了测试缺乏Bbs4是否会影响纤毛的组装和结构，我们分析了Bbs4基因敲除（Bbs4(-/-)）小鼠的初级纤毛。
通过免疫细胞化学、扫描电子显微镜和透射电子显微镜检查野生型（Bbs4(+/+)）和Bbs4(-/-)小鼠的肾小管培养物。
我们的培养条件产生了主要起源于集合管的纤毛上皮细胞。在Bbs4(-/-)细胞中，纤毛和基体的微管超微结构未出现破坏。在对照细胞中，培养7天时纤毛长度达到最大值。在Bbs4(-/-)小鼠培养的细胞中，纤毛最初较短，但在培养10天时超过了对照纤毛的长度。Bbs4(-/-)小鼠的肾初级纤毛也更长。
缺乏Bbs4不会导致纤毛或基体结构异常。然而，Bbs4(-/-)细胞中纤毛组装的动力学发生了改变，这表明Bbs4在纤毛组装调节中发挥作用。
