Differences in renal tubule primary cilia length in a mouse model of Bardet-Biedl syndrome.

Abstract

BACKGROUND: 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. METHODS: Renal tubule cultures from wild-type (Bbs4(+/+)) and Bbs4(-/-) mice were examined by immunocytochemistry and scanning and transmission electron microscopy. RESULTS: 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. CONCLUSIONS: 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.