ciBAR1 loss in mice causes laterality defects, pancreatic degeneration, and altered glucose tolerance

Bin/Amphiphysin/Rvs (BAR) domains are highly conserved domains found in all eukaryotes. BAR domain proteins form crescent-shaped dimers that sense and sculpt curved lipid membranes and play key roles in various cellular processes. However, their functions in mammalian development are poorly understood. We previously demonstrated that Chibby1-interacting BAR domain-containing 1 (ciBAR1, formerly known as FAM92A) localizes to the ciliary base and plays a critical role in ciliogenesis. Here, we report ciliopathy phenotypes of ciBAR1-KO mice. We found that ∼28% of ciBAR1-KO mice show embryonic lethality because of randomized left-right asymmetry; the rest survive into adulthood with no gross morphological abnormalities. Histological assessments of ciliated tissues revealed exocrine pancreatic lesions. Although overall endocrine islet morphology appeared to be normal, ciBAR1-KO mice showed impaired glucose tolerance. Examination of ductal and islet cilia revealed that cilia number and length were significantly reduced in ciBAR1-KO pancreata. ciBAR1-KO MEFs also exhibited ciliary defects. Our findings indicate that ciBAR1 plays a critical role in ciliogenesis depending on the tissue and cell type in mice.