A gene-targeted mouse model for chorea-acanthocytosis
| Autor: | Shu-ichi Ueno, Akira Kusumoto, Shinji Muroya, Atsu Aiba, Mio Ichiba, Emiko Mizuno, Kenji Nakamura, Akira Sano, Hiroaki Kawaguchi, Yuko Tomemori, Motoya Katsuki, Kazuki Nakao, Hiroki Yoshida, Masayuki Nakamura, Daisuke Sato |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
DNA Complementary Molecular Sequence Data Vesicular Transport Proteins Acanthocytes Nerve Tissue Proteins Striatum Biology medicine.disease_cause Biochemistry Acanthocytosis Cellular and Molecular Neuroscience Exon Mice Mice Neurologic Mutants Dopamine Chorea Internal medicine Basal ganglia medicine Animals Humans Cloning Molecular Chorea acanthocytosis Mutation Neurodegeneration Proteins Syndrome medicine.disease Mice Inbred C57BL Disease Models Animal Endocrinology Gene Targeting medicine.drug |
| Zdroj: | Journal of neurochemistry. 92(4) |
| ISSN: | 0022-3042 |
| Popis: | Chorea-acanthocytosis (CHAC) is a hereditary neurodegenerative disorder with autosomal recessive transmission, in which selective degeneration of striatum has been reported in brain pathology. Clinically, CHAC shows Huntington's disease-like neuropsychiatric symptoms and red blood cell acanthocytosis. Recently, we identified the gene, CHAC, encoding a novel protein, chorein, in which a deletion mutation was found in Japanese families with CHAC. In the present study, we have identified the mouse CHAC cDNA sequence and the exon-intron structures of the gene and produced a CHAC model mouse introducing no. 60-61 exon deletion corresponding to a human disease mutation by a gene-targeting technique. The mice began to show acanthocytosis and motor disturbance in old age. In behavioral observations, locomotor activity was significantly decreased and the contact time at social interaction test was decreased significantly in the model mice. In the brain pathology, many apoptotic cells were observed in the striatum of the mutant mice. In neurochemical determinations, the dopamine metabolite, homovanillic acid, concentration decreased significantly in the portion including the midbrain of the mutant mice. These findings are consistent with the human results reported elsewhere and indicate that the CHAC model mice showed a mild phenotype with late adult onset. The CHAC model mouse therefore provides a good model system to study the human disease. |
| Databáze: | OpenAIRE |
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