Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice

• Published in: Cell Vol. 87; no. 3; pp. 493 - 506
• Main Authors: Mangiarini, Laura, Sathasivam, Kirupa, Seller, Mary, Cozens, Barbara, Harper, Alex, Hetherington, Colin, Lawton, Martin, Trottier, Yvon, Lehrach, Hans, Davies, Stephen W, Bates, Gillian P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.1996; Elsevier
• Subjects: Animals; Brain - pathology; Disease Models, Animal; Exons - genetics; Female; Humans; Huntingtin Protein; Huntington Disease - genetics; Huntington Disease - pathology; Life Sciences; Male; Mice; Mice, Neurologic Mutants - genetics; Mice, Transgenic; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurons and Cognition; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Phenotype; Spinal Cord - pathology; Transgenes; Trinucleotide Repeats
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)81369-0

Huntington's disease (HD) is one of an increasing number of neurodegenerative disorders caused by a CAG/polyglutamine repeat expansion. Mice have been generated that are transgenic for the 5′ end of the human HD gene carrying (CAG) 115–(CAG) 150 repeat expansions. In three lines, the transgene is ubiquitously expressed at both mRNA and protein level. Transgenic mice exhibit a progressive neurological phenotype that exhibits many of the features of HD, including choreiform-like movements, involuntary stereotypic movements, tremor, and epileptic seizures, as well as nonmovement disorder components. This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies.