Gtf2i and Gtf2ird1 mutation do not account for the full phenotypic effect of the Williams syndrome critical region in mouse models.

摘要: Williams syndrome (WS) is a neurodevelopmental disorder caused by 1.5-1.8 Mbp deletion on chromosome 7q11.23, affecting the copy number of 26-28 genes. Phenotypes WS include cardiovascular problems, craniofacial dysmorphology, deficits in visual-spatial cognition and characteristic hypersocial personality. There are still no genes region that have been consistently linked to cognitive behavioral phenotypes, although human studies mouse models led current hypothesis general transcription factor 2 I family genes, GTF2I GTF2IRD1, responsible. Here we test these two factors sufficient reproduce phenotypes critical (WSCR). We compare new model with loss function mutations both Gtf2i Gtf2ird1 an established lacking complete WSCR. show (CD) has across several domains including social communication, motor functioning conditioned fear not explained Gtf2ird1. Furthermore, transcriptome profiling hippocampus shows changes synaptic CD seen double mutants. Thus, thoroughly defined set molecular consequences WSCR shown or combinations beyond necessary produce phenotypic effects.