| First Author | Ambrozkiewicz MC | Year | 2021 |
| Journal | Mol Psychiatry | Volume | 26 |
| Issue | 6 | Pages | 1980-1995 |
| PubMed ID | 32249816 | Mgi Jnum | J:333720 |
| Mgi Id | MGI:7439874 | Doi | 10.1038/s41380-020-0714-8 |
| Citation | Ambrozkiewicz MC, et al. (2021) The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc. Mol Psychiatry 26(6):1980-1995 |
| abstractText | Kaufman oculocerebrofacial syndrome (KOS) is a severe autosomal recessive disorder characterized by intellectual disability, developmental delays, microcephaly, and characteristic dysmorphisms. Biallelic mutations of UBE3B, encoding for a ubiquitin ligase E3B are causative for KOS. In this report, we characterize neuronal functions of its murine ortholog Ube3b and show that Ube3b regulates dendritic branching in a cell-autonomous manner. Moreover, Ube3b knockout (KO) neurons exhibit increased density and aberrant morphology of dendritic spines, altered synaptic physiology, and changes in hippocampal circuit activity. Dorsal forebrain-specific Ube3b KO animals show impaired spatial learning, altered social interactions, and repetitive behaviors. We further demonstrate that Ube3b ubiquitinates the catalytic gamma-subunit of calcineurin, Ppp3cc, the overexpression of which phenocopies Ube3b loss with regard to dendritic spine density. This work provides insights into the molecular pathologies underlying intellectual disability-like phenotypes in a genetically engineered mouse model. |
