title: Characterization of Behavioral, Neuropathological, Brain Metabolic and Key Molecular Changes in zQ175 Knock-In Mouse Model of Huntington's Disease.
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.
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Qi
authors: Q
authors: Peng
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Department of General Practice, The First hospital of China Medical University, Shenyang, Liaoning Province, China.
authors: Bin
authors: B
authors: Wu
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Mali
authors: M
authors: Jiang
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Jing
authors: J
authors: Jin
authors: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Zhipeng
authors: Z
authors: Hou
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Jennifer
authors: J
authors: Zheng
authors: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Jiangyang
authors: J
authors: Zhang
authors: Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Wenzhen
authors: W
authors: Duan
mesh_terms: D000818:Animals; D001284:Atrophy; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism; D009048:Motor Skills / Q000502:physiology; D059906:Neuroimaging; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse