TY - JOUR
T1 - A novel and accurate full-length HTT mouse model for Huntington’s disease
AU - Shenoy, Sushila A.
AU - Zheng, Sushuang
AU - Liu, Wencheng
AU - Dai, Yuanyi
AU - Liu, Yuanxiu
AU - Hou, Zhipeng
AU - Mori, Susumu
AU - Tang, Yi
AU - Cheng, Jerry
AU - Duan, Wenzhen
AU - Li, Chenjian
N1 - Publisher Copyright:
© Shenoy et al.
PY - 2022/1
Y1 - 2022/1
N2 - Here, we report the generation and characterization of a novel Huntington’s disease (HD) mouse model BAC226Q by using a bacterial artificial chromosome (BAC) system, expressing full-length human HTT with ~226 CAG-CAA repeats and containing endogenous human HTT promoter and regulatory elements. BAC226Q recapitulated a full-spectrum of age-dependent and progressive HD-like phenotypes without unwanted and erroneous phenotypes. BAC226Q mice developed normally, and gradually exhibited HD-like psychiatric and cognitive phenotypes at 2 months. From 3 to 4 months, BAC226Q mice showed robust progressive motor deficits. At 11 months, BAC226Q mice showed significant reduced life span, gradual weight loss and exhibiteneuropathology including significant brain atrophy specific to striatum and cortex, striatal neuronadeath, widespread huntingtin inclusions, and reactive pathology. Therefore, the novel BAC226Q mouse accurately recapitulating robust, age-dependent, progressive HD-like phenotypes will be a valuable tool for studying disease mechanisms, identifying biomarkers, and testing gene-targeting therapeutic approaches for HD.
AB - Here, we report the generation and characterization of a novel Huntington’s disease (HD) mouse model BAC226Q by using a bacterial artificial chromosome (BAC) system, expressing full-length human HTT with ~226 CAG-CAA repeats and containing endogenous human HTT promoter and regulatory elements. BAC226Q recapitulated a full-spectrum of age-dependent and progressive HD-like phenotypes without unwanted and erroneous phenotypes. BAC226Q mice developed normally, and gradually exhibited HD-like psychiatric and cognitive phenotypes at 2 months. From 3 to 4 months, BAC226Q mice showed robust progressive motor deficits. At 11 months, BAC226Q mice showed significant reduced life span, gradual weight loss and exhibiteneuropathology including significant brain atrophy specific to striatum and cortex, striatal neuronadeath, widespread huntingtin inclusions, and reactive pathology. Therefore, the novel BAC226Q mouse accurately recapitulating robust, age-dependent, progressive HD-like phenotypes will be a valuable tool for studying disease mechanisms, identifying biomarkers, and testing gene-targeting therapeutic approaches for HD.
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U2 - 10.7554/eLife.70217
DO - 10.7554/eLife.70217
M3 - Article
C2 - 35023827
AN - SCOPUS:85123565963
SN - 2050-084X
VL - 11
JO - eLife
JF - eLife
M1 - e70217
ER -