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αT-catenin in restricted brain cell types and its potential connection to autism

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Abstract
BACKGROUND: Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (αT-cat, CTNNA3) with the development of autism. Where αT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown. METHODS: We used the αT-cat knockout mouse to examine the localization of αT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss. RESULTS: We found that αT-cat comprises the ependymal cell junctions of the ventricles of the brain, and its loss led to compensatory upregulation of αE-cat expression. Notably, αT-cat was not detected within the choroid plexus, which relies on cell junction components common to typical epithelial cells. While αT-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 αT-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 αT-cat loss, such as GABA-A receptor activation. CONCLUSIONS: These findings raise the possibility that the genetic associations between αT-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.

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MLA
Folmsbee, Stephen Sai, Douglas R Wilcox, Koen Tyberghein, et al. “αT-catenin in Restricted Brain Cell Types and Its Potential Connection to Autism.” JOURNAL OF MOLECULAR PSYCHIATRY 4 (2016): n. pag. Print.
APA
Folmsbee, Stephen Sai, Wilcox, D. R., Tyberghein, K., De Bleser, P., Tourtellotte, W. G., van Hengel, J., Van Roy, F., et al. (2016). αT-catenin in restricted brain cell types and its potential connection to autism. JOURNAL OF MOLECULAR PSYCHIATRY, 4.
Chicago author-date
Folmsbee, Stephen Sai, Douglas R Wilcox, Koen Tyberghein, Pieter De Bleser, Warren G Tourtellotte, Jolanda van Hengel, Frans Van Roy, and Cara J Gottardi. 2016. “αT-catenin in Restricted Brain Cell Types and Its Potential Connection to Autism.” Journal of Molecular Psychiatry 4.
Chicago author-date (all authors)
Folmsbee, Stephen Sai, Douglas R Wilcox, Koen Tyberghein, Pieter De Bleser, Warren G Tourtellotte, Jolanda van Hengel, Frans Van Roy, and Cara J Gottardi. 2016. “αT-catenin in Restricted Brain Cell Types and Its Potential Connection to Autism.” Journal of Molecular Psychiatry 4.
Vancouver
1.
Folmsbee SS, Wilcox DR, Tyberghein K, De Bleser P, Tourtellotte WG, van Hengel J, et al. αT-catenin in restricted brain cell types and its potential connection to autism. JOURNAL OF MOLECULAR PSYCHIATRY. 2016;4.
IEEE
[1]
S. S. Folmsbee et al., “αT-catenin in restricted brain cell types and its potential connection to autism,” JOURNAL OF MOLECULAR PSYCHIATRY, vol. 4, 2016.
@article{8522270,
  abstract     = {BACKGROUND: Recent genetic association studies have linked the cadherin-based adherens junction protein alpha-T-catenin (αT-cat, CTNNA3) with the development of autism. Where αT-cat is expressed in the brain, and how its loss could contribute to this disorder, are entirely unknown.
METHODS: We used the αT-cat knockout mouse to examine the localization of αT-cat in the brain, and we used histology and immunofluorescence analysis to examine the neurobiological consequences of its loss.
RESULTS: We found that αT-cat comprises the ependymal cell junctions of the ventricles of the brain, and its loss led to compensatory upregulation of αE-cat expression. Notably, αT-cat was not detected within the choroid plexus, which relies on cell junction components common to typical epithelial cells. While αT-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 αT-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 αT-cat loss, such as GABA-A receptor activation.
CONCLUSIONS: These findings raise the possibility that the genetic associations between αT-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.},
  articleno    = {2},
  author       = {Folmsbee, Stephen Sai and Wilcox, Douglas R and Tyberghein, Koen and De Bleser, Pieter and Tourtellotte, Warren G and van Hengel, Jolanda and Van Roy, Frans and Gottardi, Cara J},
  issn         = {2049-9256},
  journal      = {JOURNAL OF MOLECULAR PSYCHIATRY},
  language     = {eng},
  pages        = {13},
  title        = {αT-catenin in restricted brain cell types and its potential connection to autism},
  url          = {http://dx.doi.org/10.1186/s40303-016-0017-9},
  volume       = {4},
  year         = {2016},
}

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