Capucin: a new molecular target for Huntington’s disease
Huntington's disease is a neurodegenerative disorder characterised by the atrophy of two brain structures, the caudate nucleus and the putamen. Although the cause of the disease is known (mutation of a gene expressed in all brain regions), the mechanisms that culminate in the selective degeneration of these structures remain unexplained.
In the course of a large-scale search for molecular markers of brain regions in the mouse, a team at the CEA identified a gene chiefly expressed in the caudate nucleus and the putamen.
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In situ hybridisation of a mouse brain coronal section with a probe recognising the Capucin messenger RNA. The hybridization signal appears as a violet precipitate. Acb: nucleus accumbens, CPu: caudate nucleus-putamen. |
This gene, for which no complete sequence was hitherto available in data bases, encodes a protein that lacks any homology with proteins of known function. Because of the specific gene expression pattern, the protein has been named Capucin, standing for 'caudate-putamen protein'.
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The authors also demonstrates that the expression of the Capucin gene strikingly diminishes in two mouse models of Huntington's disease, well before neuronal degeneration is observed. It has also been found that the expression level of a certain number of genes diminish in these two brain regions. |
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Expression level of Capucin messenger RNA in the caudate nucleus-putamen of control mice (1) and a transgenic mouse model of Huntington's disease (2), and in cultures of caudate nucleus-putamen of rats infected by a lentivirus bearing a normal form (3) or a mutant form (4) of the gene responsible for Huntington's disease.
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These findings suggest that the functions of these brain structures may be specifically affected in the earliest stages of Huntington's disease, through a regulatory mechanism common to different genes.