| First Author | Boy J | Year | 2009 |
| Journal | Hum Mol Genet | Volume | 18 |
| Issue | 22 | Pages | 4282-95 |
| PubMed ID | 19666958 | Mgi Jnum | J:154079 |
| Mgi Id | MGI:4367173 | Doi | 10.1093/hmg/ddp381 |
| Citation | Boy J, et al. (2009) Reversibility of symptoms in a conditional mouse model of spinocerebellar ataxia type 3. Hum Mol Genet 18(22):4282-95 |
| abstractText | Spinocerebellar ataxia type 3 (SCA3) is caused by the expansion of a CAG repeat tract that affects the MJD1 gene which encodes the ataxin-3 protein. In order to analyze whether symptoms caused by ataxin-3 with an expanded repeat are reversible in vivo, we generated a conditional mouse model of SCA3 using the Tet-Off system. We used a full-length human ataxin-3 cDNA with 77 repeats in order to generate the responder mouse line. After crossbreeding with a PrP promoter mouse line, double transgenic mice developed a progressive neurological phenotype characterized by neuronal dysfunction in the cerebellum, reduced anxiety, hyperactivity, impaired Rotarod performance and lower body weight gain. When ataxin-3 expression was turned off in symptomatic mice in an early disease state, the transgenic mice were indistinguishable from negative controls after 5 months of treatment. These results show that reducing the production of pathogenic ataxin-3 indeed may be a promising approach to treat SCA3, provided that such treatment is applied before irreversible damage has taken place and that it is continued for a sufficiently long time. |
