title: Similar striatal gene expression profiles in the striatum of the YAC128 and HdhQ150 mouse models of Huntington's disease are not reflected in mutant Huntingtin inclusion prevalence.
abstract: BACKGROUND
  The YAC128 model of Huntington's disease (HD) shows substantial deficits in motor, learning and memory tasks and alterations in its transcriptional profile. We examined the changes in the transcriptional profile in the YAC128 mouse model of HD at 6, 12 and 18 months and compared these with those seen in other models and human HD caudate.
  
  
  RESULTS
  Differential gene expression by genotype showed that genes related to neuronal function, projection outgrowth and cell adhesion were altered in expression. A Time-course ANOVA revealed that genes downregulated with increased age in wild-type striata were likely to be downregulated in the YAC128 striata. There was a substantial overlap of concordant gene expression changes in the YAC128 striata compared with those in human HD brain. Changes in gene expression over time showed fewer striatal YAC128 RNAs altered in abundance than in the HdhQ150 striata but there was a very marked overlap in transcriptional changes at all time points. Despite the similarities in striatal expression changes at 18 months the HdhQ150 mice showed widespread mHTT and ubiquitin positive inclusion staining in the striatum whereas this was absent in the YAC128 striatum.
  
  
  CONCLUSIONS
  The gene expression changes in YAC128 striata show a very closely matched profile to that of HdhQ150 striata and are already significantly different between genotypes by six months of age, implying that the temporal molecular gene expression profiles of these models match very closely, despite differences in the prevalence of brain inclusion formation between the models. The YAC128 gene expression changes appear to correlate well with gene expression differences caused by ageing. A relatively small number of genes showed significant differences in expression between the striata of the two models and these could explain some of the phenotypic differences between the models.
authors.affiliation: Brain Research Group, School of Bioscience, Cardiff University, Cardiff, CF10 4AX, UK. bayram-westonz@cf.ac.uk.
authors.forename: Zubeyde
authors.initials: Z
authors.lastname: Bayram-Weston
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK. stonetc@cf.ac.uk.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Stone
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK. gilespj@cf.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Giles
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK. ellistonla@cf.ac.uk.
authors.forename: Linda
authors.initials: L
authors.lastname: Elliston
authors.affiliation: Brain Research Group, School of Bioscience, Cardiff University, Cardiff, CF10 4AX, UK. n.janghra@ucl.ac.uk.
authors.forename: Nari
authors.initials: N
authors.lastname: Janghra
authors.affiliation: Brain Research Group, School of Bioscience, Cardiff University, Cardiff, CF10 4AX, UK. pduck.gemgem@googlemail.com.
authors.forename: Gemma V
authors.initials: GV
authors.lastname: Higgs
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK. holmanspa@cf.ac.uk.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Holmans
authors.affiliation: Brain Research Group, School of Bioscience, Cardiff University, Cardiff, CF10 4AX, UK. dunnettsb@cf.ac.uk.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
authors.affiliation: Brain Research Group, School of Bioscience, Cardiff University, Cardiff, CF10 4AX, UK. brookssp@cf.ac.uk.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Brooks
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, CF24 4HQ, UK. jonesl1@cf.ac.uk.
authors.forename: Lesley
authors.initials: L
authors.lastname: Jones
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D015995:Prevalence; D059467:Transcriptome