Principle Investigator: Rolf Stottmann, PhD

Rolf Stottmann.The genetic basis for variability in human disease is still a mysterious phenomenon. Ciliopathies – developmental and degenerative single-gene disorders that result from deficits in cilia within a cell − are one set of disorders with such variability. Cilia are now known to perform a number of crucial roles from fluid clearance to cell signalling within key developmental pathways. Bardet-Biedl syndrome (BBS) is a canonical ciliopathy, usually presenting with symptoms including obesity, vision loss, kidney malformation, extra fingers or toes, intellectual disability, and the loss of smell. However, the range of characterizations in BBS and other related ciliopathies can be quite broad. This is likely due to unidentified genetic modifiers. The mouse can be a tractable model to study this problem by taking advantage of the power of inbred strain genetics.

We have mouse models of two BBS genes: Bbs7 and Bbs10. In both cases, we note a marked difference in survival of mice between two distinct inbred strains. We will use modern genomic tools to identify areas on the genome that explain these differences. We can ultimately use these findings to identify ways to alter the severity of ciliopathies in future patients. The ability to modify the trajectory of a ciliopathy would be a powerful therapeutic intervention.