Behavioral and brain phenotypes of mouse models of Bardet-Biedl Syndrome

The primary cilium is a microtubule-based membranous projection on the cell that is involved in multiple physiological functions. Patients who have cilia dysfunction commonly have issues with cognition, including intellectual disability. However, it is not known how cilia affect behavior. Studying mouse models of a cilia-based intellectual disability can provide insight into learning and memory. One such cilia-based intellectual disability is Bardet-Biedl Syndrome (BBS), which is caused by homozygous and compound heterozygous mutations of BBS genes. We found that a mouse model of BBS (Bbs1^M390R/M390R mice) has impaired anxiety like-behavior. In addition, we found that Bbs1^M390R/M390R mice have robust learning and memory defects. In addition, we found that other mouse models of BBS have similar learning and memory defects. These BBS mouse models have difficulty associating an environment with an aversive stimulus, a task designed to test context fear memory. This type of memory involves the hippocampus. We found that Bbs1^M390R/M390R mice have decreased cell production in the hippocampus. Treating Bbs1^M390R/M390R mice with a compound (lithium) that increases cell production in the hippocampus improved the learning and memory deficits. Our results demonstrate a potential role for cilia in learning and memory, and indicate that lithium is a potential treatment, requiring further study, for the intellectual disability phenotype of BBS.