Transgenic models and subcellular pathology — do they tell us what goes wrong in Huntington's disease?

Abstract

Studies of a transgenic mouse model of Huntington's disease have led to the identification of protein deposits in neuronal nuclei in CAG repeat expansion diseases. The relationship between neuropathology and these nuclear inclusions points to their possible role in pathogenesis.

Brain Neurotransmitter Deficits in Mice Transgenic for the Huntington’s Disease Mutation

“…In the absence of the relatively selective atrophy of the greater part of striatal tissue that occurs in HD, this is not so surprising. Thus, it is perhaps important to consider other differences between the transgenic animal and the human disease (Reynolds and Dalton, 1998). In addition to the obvious factor of species, the transgenic mouse has a much longer repeat length than is commonly found in HD, and the expressed polyglutamine is in a protein that is the product of a single exon from a 67‐exon gene.…”

“…At this time the size of the brain begins to decrease, although in contrast to HD the atrophy appears initially not to be selective for any particular brain structure(s); by 16 weeks, however, selective neurodegeneration occurring in the frontal cortex, dorsal striatum, and Purkinje cells of the cerebellar vermis is apparent (M. Turmaine et al, submitted for publication). Some similarities and discrepancies between the transgenic model and the human disease have been discussed in a recent review (Reynolds and Dalton, 1998).…”