Characterization of behavioral, neuropathological, brain metabolic and key molecular changes in zQ175 knock-in mouse model of huntington's disease

Qi Peng, Bin Wu, Mali Jiang, Jing Jin, Zhipeng Hou, Jennifer Zheng, Jiangyang Zhang, Wenzhen Duan

Research output: Contribution to journalArticle

Abstract

Huntington's disease (HD) is caused by an expansion of the trinucleotide poly (CAG) tract located in exon 1 of the huntingtin (Htt) gene leading to progressive neurodegeneration in selected brain regions, and associated functional impairments in motor, cognitive, and psychiatric domains. Since the discovery of the gene mutation that causes the disease, mouse models have been developed by different strategies. Recently, a new model, the zQ175 knock-in (KI) line, was developed in an attempt to have the Htt gene in a context and causing a phenotype that more closely mimics HD in humans. The behavioral phenotype was characterized across the independent laboratories and important features reminiscent of human HD are observed in zQ175 mice. In the current study, we characterized the zQ175 model housed in an academic laboratory under reversed dark-light cycle, including motor function, in vivo longitudinal structural MRI imaging for brain volume, MRS for striatal metabolites, neuropathology, as well as a panel of key disease marker proteins in the striatum at different ages. Our results suggest that homozygous zQ175 mice exhibited significant brain atrophy before the motor deficits and brain metabolite changes. Altered striatal medium spiny neuronal marker, postsynaptic marker protein and complement component C1qC also characterized zQ175 mice. Our results confirmed that the zQ175 KI model is valuable in understanding of HD-like pathophysiology and evaluation of potential therapeutics. Our data also provide suggestions to select appropriate outcome measurements in preclinical studies using the zQ175 mice.

Original languageEnglish (US)
Article numbere0148839
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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Huntington Disease
Brain
animal models
brain
mice
Corpus Striatum
human diseases
Genes
metabolites
Metabolites
neuropathology
phenotype
genes
Phenotype
pathophysiology
atrophy
exons
Photoperiod
Genetic Association Studies
complement

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Characterization of behavioral, neuropathological, brain metabolic and key molecular changes in zQ175 knock-in mouse model of huntington's disease. / Peng, Qi; Wu, Bin; Jiang, Mali; Jin, Jing; Hou, Zhipeng; Zheng, Jennifer; Zhang, Jiangyang; Duan, Wenzhen.

In: PLoS One, Vol. 11, No. 2, e0148839, 01.02.2016.

Research output: Contribution to journalArticle

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