A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H/+) mouse.
A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H/+) mouse.
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DOI：
10.1002/mus.23522
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发表时间：
2013-02
期刊：
影响因子：
3.4
通讯作者：
Kimonis, Virginia E.
中科院分区：
文献类型：
--
作者：
Nalbandian, Angele;Llewellyn, Katrina J.;Badadani, Mallikarjun;Yin, Hong Z.;Nguyen, Christopher;Katheria, Veeral;Watts, Giles;Mukherjee, Jogeshwar;Vesa, Jouni;Caiozzo, Vincent;Mozaffar, Tahseen;Weiss, John H.;Kimonis, Virginia E.
关键词：
valosin containing protein （VCP）基因突变可导致遗传性包涵体肌病（hIBM），并伴有骨Paget病（PDB）和额颞叶痴呆（FTD）。最近，他们与2%的家族性ALS病例有关。敲入小鼠模型为研究vcp相关的发病机制提供了机会。对VCPR155H/+敲入小鼠模型进行肌力、免疫组化、Western、细胞凋亡、自噬和MicroPET/CT成像分析。VCPR155H/+小鼠出现明显的进行性肌肉无力，股四头肌和大脑出现进行性细胞质TDP-43、泛素阳性包体积累和LC3-II染色升高。显微ct分析显示长骨末端有佩吉特样病变。脊髓表现为神经退行性改变，运动神经元泛素和TDP-43病理。VCPR155H/+敲入小鼠是了解vcp相关疾病机制和未来治疗的良好临床前模型。
Mutations in the valosin containing protein (VCP) gene cause hereditary Inclusion Body Myopathy (hIBM) associated with Paget disease of bone (PDB), and frontotemporal dementia (FTD). More recently they have been linked to 2% of familial ALS cases. A knock-in mouse model offers the opportunity to study VCP-associated pathogenesis. The VCPR155H/+ knock-in mouse model was assessed for muscle strength, immunohistochemical, Western, apoptosis, autophagy and MicroPET/CT imaging analyses. VCPR155H/+ mice developed significant progressive muscle weakness, and the quadriceps and brain developed progressive cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-II staining. MicroCT analyses revealed Paget-like lesions at the ends of long bones. Spinal cord demonstrated neurodegenerative changes, ubiquitin, and TDP-43 pathology of motor neurons. VCPR155H/+ knock-in mice represent an excellent pre-clinical model for understanding VCP-associated disease mechanisms and future treatments.
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影响因子：
7.8
作者：
Fu, Xinrong;Ng, Christine;Feng, Daorong;Liang, Chun
通讯作者：
Liang, Chun
DOI：
10.1038/nsb972
发表时间：
2003-10-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
DeLaBarre, B;Brunger, AT
通讯作者：
Brunger, AT
影响因子：
12.4
作者：
Hirabayashi, M;Inoue, K;Kakizuka, A
通讯作者：
Kakizuka, A
DOI：
10.1196/annals.1396.020
发表时间：
2007-01-01
期刊：
HEALTHY AGING AND LONGEVITY
影响因子：
--
作者：
Bergamini, Ettore;Cavallini, Gabriella;Gori, Zina
通讯作者：
Gori, Zina
影响因子：
2.1
作者：
Dell'Atti, C.;Cassar-Pullicino, V. N.;Lalam, R. K.;Tins, B. J.;Tyrrell, P. N. M.
通讯作者：
Tyrrell, P. N. M.