| Experiment Id | GSE213354 | Name | Transcriptome analysis of Adnp-heterozygous mice in the hippocampus |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-07-25 |
| description | ADNP syndrome, involving the ADNP transcription factor in the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). In ASD, ADNP is a highly penetrant risk gene, accounting for ~0.17% cases. Although Adnp-haploinsufficient mice display various phenotypic deficits, the underlying synaptic mechanisms are poorly understood. Here we report age-differential synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIalpha hyperactivity in Adnp-mutant mice. These mice show impaired and inflexible contextual learning and memory additional to social and anxiety-related deficits in adults long after a marked decrease in ADNP protein levels to ~10% of newborn levels in juveniles. In addition, Adnp-mutant adults show abnormally enhanced long-term potentiation in adults but not in juveniles. This accompanies CaMKIIalpha hyperactivity involving increased baseline autophosphorylation, as revealed by unbiased proteomic analyses. Therefore, ADNP haploinsufficiency in mice leads to cognitive inflexibility involving altered synaptic plasticity and signaling in adults long after a marked decrease in Adnp expression in juveniles. Transcriptome analysis of Adnp-heterozygous mice in the hippocampus of adults and juveniles. |
