| First Author | La Spada AR | Year | 2001 |
| Journal | Neuron | Volume | 31 |
| Issue | 6 | Pages | 913-27 |
| PubMed ID | 11580893 | Mgi Jnum | J:71971 |
| Mgi Id | MGI:2151323 | Doi | 10.1016/s0896-6273(01)00422-6 |
| Citation | La Spada AR, et al. (2001) Polyglutamine-expanded ataxin-7 antagonizes crx function and induces cone-rod dystrophy in a mouse model of sca7. (Erratum: Neuron 2001;32:957). Neuron 31(6):913-27 |
| abstractText | Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a CAG repeat expansion. To determine the mechanism of neurotoxicity, we produced transgenic mice and observed a cone-rod dystrophy. Nuclear inclusions were present, suggesting that the disease pathway involves the nucleus. When yeast two-hybrid assays indicated that cone-rod homeobox protein (CRX) interacts with ataxin-7, we performed further studies to assess this interaction. We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation. In SCA7 transgenic mice, electrophoretic mobility shift assays indicated reduced CRX binding activity, while RT-PCR analysis detected reductions in CRX-regulated genes. Our results suggest that CRX transcription interference accounts for the retinal degeneration in SCA7 and thus may provide an explanation for how cell-type specificity is achieved in this polyglutamine repeat disease. |
