Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment.

Longitudinal evaluation of the Hdh(CAG)150 knock-in murine model of Huntington's disease.

Heng MY, Tallaksen-Greene SJ, Detloff PJ, Albin RL

Neuroscience Graduate Program and Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.

Several murine genetic models of Huntington's disease (HD) have been developed. Murine genetic models are crucial for identifying mechanisms of neurodegeneration in HD and for preclinical evaluation of possible therapies for HD. Longitudinal analysis of mutant phenotypes is necessary to validate models and to identify appropriate periods for analysis of early events in the pathogenesis of neurodegeneration. Here we report longitudinal characterization of the murine Hdh(CAG)150 knock-in model of HD. A series of behavioral tests at five different time points (20, 40, 50, 70, and 100 weeks) demonstrates an age-dependent, late-onset behavioral phenotype with significant motor abnormalities at 70 and 100 weeks of age. Pathological analysis demonstrated loss of striatal dopamine D1 and D2 receptor binding sites at 70 and 100 weeks of age, and stereological analysis showed significant loss of striatal neuron number at 100 weeks. Late-onset behavioral abnormalities, decrease in striatal dopamine receptors, and diminished striatal neuron number observed in this mouse model recapitulate key features of HD. The Hdh(CAG)150 knock-in mouse is a valid model to evaluate early events in the pathogenesis of neurodegeneration in HD.

Published 23 August 2007 in J Neurosci, 27(34): 8989-98.
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