Peripheral huntingtin silencing does not ameliorate central signs of disease in the B6.HttQ111/+ mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD.

Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.Htt model of Huntington's disease.

We investigated the appearance and progression of disease-relevant signs in the B6.Htt mouse, a genetically precise model of the mutation that causes Huntington's disease (HD). We find that B6.