Bbs1 gene is required for wound healing (216.5)

Abstract

Bardet‐Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder associated with several features including obesity, polydactyly, retinal degeneration, hypogenitalism, leaning difficulty and renal dysfunction. Mice bearing an M390R mutation in Bbs1 gene (which a common mutation in human BBS) recapitulates many BBS phenotypes including obesity and hypogenitalism. However, the role and contribution of Bbs1 gene to cell migration and tissue repair remains unclear. Using wound healing assays, we found that cultured mouse embryonic fibroblasts (MEFs) derived from Bbs1M390R knock‐in mice have severely compromised migratory ability compared to the MEF derived from wild type mice. Activation of AKT by platelet‐derived growth factor‐AA (PDGF‐AA) was also markedly reduced in Bbs1M390R MEF, suggesting that decreased PDGFRα signaling contributes to the migratory defects. Immunofluorescence microscopy analysis with acetylated α‐tubulin showed that both wt and BBS1‐Ki MEFs form primary cilia. The primary cilia were oriented towards the leading edge of the wound in wt MEFs. In marked contrast, primary cilia of BBs‐KI MEFs appeared randomly positioned and lacked an axis of orientation towards the edge of the wound. Furthermore, in vivo wound healing assays showed defects in Bbs1M390R knock‐in mouse compared to control littermates. These findings demonstrate that the Bbs1 gene is required for migration and tissue repairs.Grant Funding Source: NIH and AHA