| First Author | Ban Y | Year | 2022 |
| Journal | Exp Neurol | Volume | 347 |
| Pages | 113880 | PubMed ID | 34597683 |
| Mgi Jnum | J:321396 | Mgi Id | MGI:6854464 |
| Doi | 10.1016/j.expneurol.2021.113880 | Citation | Ban Y, et al. (2022) Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism. Exp Neurol 347:113880 |
| abstractText | Epilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1(PK1) gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PK1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a PK1(R104Q) mouse line. The mutant mice showed reduced density of excitatory synapses in hippocampus and impaired interaction between PK1 and the repressor element 1(RE-1) silencing transcription factor (REST). They also displayed reduced seizure threshold, impaired social interaction, and cognitive functions. Taken together, the PK1(R104Q) mice display characteristic behavioral features similar to the key symptoms of epilepsy and ASD, providing a useful model for studying the molecular and neural circuit mechanisms underlying the comorbidity of epilepsy and ASD. |
