| First Author | Folmsbee SS | Year | 2016 |
| Journal | J Mol Psychiatry | Volume | 4 |
| Pages | 2 | PubMed ID | 27330745 |
| Mgi Jnum | J:244966 | Mgi Id | MGI:5913745 |
| Doi | 10.1186/s40303-016-0017-9 | Citation | Folmsbee SS, et al. (2016) alphaT-catenin in restricted brain cell types and its potential connection to autism. J Mol Psychiatry 4:2 |
| abstractText | BACKGROUND: Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (alphaT-cat, CTNNA3) with the development of autism. Where alphaT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown. METHODS: We used the alphaT-cat knockout mouse to examine the localization of alphaT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss. RESULTS: We found that alphaT-cat comprises the ependymal cell junctions of the ventricles of the brain, and its loss led to compensatory upregulation of alphaE-cat expression. Notably, alphaT-cat was not detected within the choroid plexus, which relies on cell junction components common to typical epithelial cells. While alphaT-cat was not detected in neurons of the cerebral cortex, it was abundantly detected within neuronal structures of the molecular layer of the cerebellum. Although alphaT-cat loss led to no overt differences in cerebral or cerebellar structure, RNA-sequencing analysis from wild type versus knockout cerebella identified a number of disease-relevant signaling pathways associated with alphaT-cat loss, such as GABA-A receptor activation. CONCLUSIONS: These findings raise the possibility that the genetic associations between alphaT-cat and autism may be due to ependymal and cerebellar defects, and highlight the potential importance of a seemingly redundant adherens junction component to a neurological disorder. |
