Rodent genetic models of Huntington disease

Huntington disease (HD) is a dominantly inherited human neurodegenerative disorder characterized by motor deficits, cognitive impairment, and psychiatric symptoms leading to inexorable decline and death. Since the identification of the huntingtin gene and the characteristic expanded CAG repeat/polyglutamine mutation, multiple murine genetic models and one rat genetic model have been generated. These models fall into two general categories: transgenic models with ectopic expression of the characteristic expanded CAG codon mutation, and knock-in models with expression of mutant huntingtin under control of endogenous regulatory elements. Rodent genetic models are valuable tools for studying mechanisms of pathogenesis in HD and for preclinical evaluation of possible therapies. In this mini-review, we provide a concise comparative summary of rodent genetic models of HD. (C) 2008 Elsevier Inc. All rights reserved.