| First Author | Gao Y | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 46 | Pages | 16581-90 |
| PubMed ID | 22090485 | Mgi Jnum | J:177913 |
| Mgi Id | MGI:5296690 | Doi | 10.1523/JNEUROSCI.3332-11.2011 |
| Citation | Gao Y, et al. (2011) beta-III Spectrin Is Critical for Development of Purkinje Cell Dendritic Tree and Spine Morphogenesis. J Neurosci 31(46):16581-90 |
| abstractText | Mutations in the gene encoding beta-III spectrin give rise to spinocerebellar ataxia type 5, a neurodegenerative disease characterized by progressive thinning of the molecular layer, loss of Purkinje cells and increasing motor deficits. A mouse lacking full-length beta-III spectrin (beta-III(-/-)) displays a similar phenotype. In vitro and in vivo analyses of Purkinje cells lacking beta-III spectrin, reveal a critical role for beta-III spectrin in Purkinje cell morphological development. Disruption of the normally well ordered dendritic arborization occurs in Purkinje cells from beta-III(-/-) mice, specifically showing a loss of monoplanar organization, smaller average dendritic diameter and reduced densities of Purkinje cell spines and synapses. Early morphological defects appear to affect distribution of dendritic, but not axonal, proteins. This study confirms that thinning of the molecular layer associated with disease pathogenesis is a consequence of Purkinje cell dendritic degeneration, as Purkinje cells from 8-month-old beta-III(-/-) mice have drastically reduced dendritic volumes, surface areas and total dendritic lengths compared with 5- to 6-week-old beta-III(-/-) mice. These findings highlight a critical role of beta-III spectrin in dendritic biology and are consistent with an early developmental defect in beta-III(-/-) mice, with abnormal Purkinje cell dendritic morphology potentially underlying disease pathogenesis. |
