| First Author | Armbrust KR | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 30 | Pages | 9891-904 |
| PubMed ID | 25057192 | Mgi Jnum | J:215593 |
| Mgi Id | MGI:5605891 | Doi | 10.1523/JNEUROSCI.0876-14.2014 |
| Citation | Armbrust KR, et al. (2014) Mutant beta-III spectrin causes mGluR1alpha mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5. J Neurosci 34(30):9891-904 |
| abstractText | Spinocerebellar ataxia type 5 (SCA5), a dominant neurodegenerative disease characterized by profound Purkinje cell loss, is caused by mutations in SPTBN2, a gene that encodes beta-III spectrin. SCA5 is the first neurodegenerative disorder reported to be caused by mutations in a cytoskeletal spectrin gene. We have developed a mouse model to understand the mechanistic basis for this disease and show that expression of mutant but not wild-type beta-III spectrin causes progressive motor deficits and cerebellar degeneration. We show that endogenous beta-III spectrin interacts with the metabotropic glutamate receptor 1alpha (mGluR1alpha) and that mice expressing mutant beta-III spectrin have cerebellar dysfunction with altered mGluR1alpha localization at Purkinje cell dendritic spines, decreased mGluR1-mediated responses, and deficient mGluR1-mediated long-term potentiation. These results indicate that mutant beta-III spectrin causes mislocalization and dysfunction of mGluR1alpha at dendritic spines and connects SCA5 with other disorders involving glutamatergic dysfunction and synaptic plasticity abnormalities. |
