Modeling Huntington's disease in cells, flies, and mice

• Published in: Molecular neurobiology 2001-02, Vol.23 (1), p.21-51
• Main Authors: Sipione, S, Cattaneo, E
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Apoptosis - physiology; Caenorhabditis elegans; Cell Line, Transformed - metabolism; Cells, Cultured - metabolism; Cells, Cultured - pathology; Corpus Striatum - metabolism; Corpus Striatum - pathology; Cysteine Endopeptidases - physiology; Disease Models, Animal; Drosophila melanogaster; Embryonic and Fetal Development - genetics; Fetal Proteins - physiology; Genes; Genes, Dominant; Genes, Lethal; Haplorhini; Humans; Huntingtin Protein; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Huntingtons disease; Kidney; Mice; Mice, Knockout; Mice, Transgenic; N-Methylaspartate - pharmacology; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurons; Neurons - metabolism; Neurons - pathology; Nuclear Proteins - chemistry; Nuclear Proteins - deficiency; Nuclear Proteins - genetics; Nuclear Proteins - physiology; PC12 Cells - metabolism; Peptide Fragments - genetics; Protein Interaction Mapping; Proteins; Rats; Studies; Trinucleotide Repeats
• ISSN: 0893-7648; 0893-7648; 1559-1182
• DOI: 10.1385/MN:23:1:21

A milestone in Huntington's disease (HD) research is represented by the identification of the causative gene. With the genetics at hand, a series of transgenic cellular and animal models has been developed, which has greatly contributed to understanding of HD. All these models are described in this review, and are compared to each other, along with the information they have generated. Although the mechanism by which progressive loss of striatal neurons occurs in HD remains uncertain, hypotheses on mutant huntingtin toxicity involve impaired vescicular trafficking, transcriptional dysregulation, and/or activation of apoptotic pathways. The development of inducible HD mice has shown that neurodegeneration in HD may be at least partially blocked. Although traditionally considered a "gain-of-function" disease, the recent finding that normal huntingtin has an important role in neuronal survival suggests that loss of function of the normal protein might contribute to HD as well, also discloseing new perspectives on the therapeutical approach to the pathology.