UC San Diego

The Wnt signaling pathways play important roles in many developmental processes from invertebrate to vertebrate. The Wnt/Planar cell polarity (PCP) pathway is one of the non- canonical Wnt signaling pathways that mainly regulate cytoskeleton. Without the control of PCP components, Drosophila wing epithelia would grow in random directions. Our lab previous work has shown that PCP components Celsr3, Vangl2 and Frizzled3 are responsible for neuronal migration, axon guidance and synapse formation. Prickle is one of the core components of PCP signaling pathway. Studies have reported that several neurological abnormalities were identified with Prickle mutation in human, mice, zebrafish and Drosophila. Prickle1 R104Q missense mutation was reported in three consanguineous families with Progressive Myoclonus Epilepsy-Ataxia Syndrome. Here, we used CRISPR-Cas 9 gene editing to generate this human point mutation in mice. In this thesis, we performed examination of behavioral deficits in Prickle1 R104Q mutant mice. We found that Prickle1 R104Q mutant mice have normal locomotor activity in open field assay and light-dark transition assay, while they exhibited deficit in novel object recognition test. Then we used three-chamber social interaction test and found that these Prickle1 mutant mice have abnormal sociability and normal social novelty. Using Barnes maze, we showed Prickle1 mutant mice have normal learning ability and spatial memory. In conclusion, our work has identified behavioral deficits in Prickle1 R104Q mutant mice.