Abstract:
:In a recent study, we reported in vivo evidence of early and sustained alterations of autophagy markers in a novel knock-in mouse model of Huntington disease (HD). The novel model is derived from selective breeding of HdhQ150 knock-in mice to generate mice with ~200 CAG/polyglutamine repeats (HdhQ200). HdhQ200 knockin mice exhibit an accelerated and more robust motor phenotype than the parent line with detectable abnormalities at 50 weeks and substantial impairments at 80 weeks. Heterozygous HdhQ200 knock-in mice accumulate htt aggregates as cytoplasmic aggregation foci (AF) as early as 9 weeks of age followed by striatal neuronal intranuclear inclusions (NIIs) by 20 weeks. By 40 weeks, striatal AF are perinuclear and immunoreactive for ubiquitin and the autophagosome marker LC3. Increased LC3-II protein expression is noted at 9 weeks and sustained throughout the disease course, and is paralleled by increased expression of p62. Early and sustained expression of: autophagy-related proteins in this genetically precise mouse model of HD suggests that alteration of autophagic flux is an important and early component of neuronal response to polyglutamine expanded huntingtin.
journal_name
Autophagyjournal_title
Autophagyauthors
Heng MY,Detloff PJ,Paulson HL,Albin RLdoi
10.4161/auto.6.8.13617subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1206-8issue
8eissn
1554-8627issn
1554-8635pii
13617journal_volume
6pub_type
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