SCA1 transgenic mice: A model for neurodegeneration caused by an expanded CAG trinucleotide repeat
| Autor: | Toni Matilla, Wael S. Yunis, Huda Y. Zoghbi, Harry T. Orr, Antonio Servadio, Rodney M. Feddersen, Lisa A. Duvick, Eric N. Burright, H. Brent Clark |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Genetically modified mouse
congenital hereditary and neonatal diseases and abnormalities Spinocerebellar Ataxia Type 1 Ataxia Molecular Sequence Data Purkinje cell Gene Expression Ataxin 1 Mice Transgenic Nerve Tissue Proteins General Biochemistry Genetics and Molecular Biology Mice Purkinje Cells Cerebellum medicine Animals RNA Messenger education Ataxin-1 Repetitive Sequences Nucleic Acid Spinocerebellar Degenerations education.field_of_study Base Sequence biology Biochemistry Genetics and Molecular Biology(all) Neurodegeneration Nuclear Proteins medicine.disease Immunohistochemistry Molecular biology Disease Models Animal Phenotype medicine.anatomical_structure Ataxins Nerve Degeneration biology.protein Atrophin-1 medicine.symptom Trinucleotide repeat expansion |
| Zdroj: | Cell. 82:937-948 |
| ISSN: | 0092-8674 |
| Popis: | Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant inherited disorder characterized by degeneration of cerebellar Purkinje cells, spinocerebellar tracts, and selective brainstem neurons owing to the expansion of an unstable CAG trinucleotide repeat. To gain insight into the pathogenesis of the SCA1 mutation and the intergenerational stability of trinucleotide repeats in mice, we have generated transgenic mice expressing the human SCA1 gene with either a normal or an expanded CAG tract. Both transgenes were stable in parent to offspring transmissions. While all six transgenic lines expressing the unexpanded human SCA1 allele had normal Purkinje cells, transgenic animals from five of six lines with the expanded SCA1 allele developed ataxia and Purkinje cell degeneration. These data indicate that expanded CAG repeats expressed in Purkinje cells are sufficient to produce degeneration and ataxia and demonstrate that a mouse model can be established for neurodegeneration caused by CAG repeat expansions. |
| Databáze: | OpenAIRE |
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