title: Onset and progression of behavioral and molecular phenotypes in a novel congenic R6/2 line exhibiting intergenerational CAG repeat stability.
abstract: In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relatively stable line of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in motor, cognitive and psychiatric-related phenotypes as well as the progression of disease-related impairments from 4 to 10 weeks of age. 110Q mice exhibited many of the phenotypes commonly associated with the R6/2 model including reduced activity and impairments in rotarod performance. The onset of many of the phenotypes occurred around 6 weeks and was progressive across age. In addition, some phenotypes were observed in mice as early as 4 weeks of age. The present study also reports the onset and progression of changes in several molecular phenotypes in the novel R6/2 mice and the association of these changes with behavioral symptom onset and progression. Data from TR-FRET suggest an association of mutant protein state changes (soluble versus aggregated) in disease onset and progression.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Randi-Michelle
authors.initials: RM
authors.lastname: Cowin
authors.forename: Nghiem
authors.initials: N
authors.lastname: Bui
authors.forename: Deanna
authors.initials: D
authors.lastname: Graham
authors.forename: Jennie R
authors.initials: JR
authors.lastname: Green
authors.forename: Stephan
authors.initials: S
authors.lastname: Grueninger
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Yuva-Paylor
authors.forename: Arsalan U
authors.initials: AU
authors.lastname: Syed
authors.forename: Andreas
authors.initials: A
authors.lastname: Weiss
authors.forename: Richard
authors.initials: R
authors.lastname: Paylor
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D019076:Transgenes; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins