The primary cilium is an organelle with a central role in cellular signal perception. Mutations in genes that encode cilia-associated proteins result in a collection of human syndromes collectively termed ciliopathies. Of these, the Bardet-Biedl syndrome (BBS) is considered one of the archetypical ciliopathies, as patients exhibit virtually all respective clinical phenotypes, such as pathological changes of the retina or the kidney. However, the behavioral phenotype associated with ciliary dysfunction has received little attention thus far. Here, we extensively characterized the behavior of two rodent models of BBS, Bbs6/Mkks, and Bbs8/Ttc8 knockout mice concerning social behavior, anxiety, and cognitive abilities. While learning tasks remained unaffected due to the genotype, we observed diminished social behavior and altered communication. Additionally, Bbs knockout mice displayed reduced anxiety. This was not due to altered adrenal gland function or corticosterone serum levels. However, hypothalamic expression of Lsamp, the limbic system associated protein, and Adam10, a protease acting on Lsamp, were reduced. This was accompanied by changes in characteristics of adult hypothalamic neurosphere cultures. In conclusion, we provide evidence that behavioral changes in Bbs knockout mice are mainly found in social and anxiety traits and might be based on an altered architecture of the hypothalamus.
Keywords: ADAM10; Bardet-Biedl syndrome; Lsamp; MRI; behavior; hypothalamus; primary cilium.