A progressive translational mouse model of human valosin‐containing protein disease: The VCPR155H/+ mouse. Issue 2 (21st November 2012)

• Record Type: Journal Article
• Authors: Nalbandian, Angèle; 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.
• Is Part Of: Muscle & nerve. Volume 47:Issue 2(2013:Feb.)
• Page Start: 260
• Page End: 270
• Publication Date: 2012-11-21
• Subjects: Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.23522
• Languages: English
• ISSNs: 0148-639X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Introduction:</title> <p>Mutations in the <italic>valosin‐containing protein (VCP)</italic> gene cause hereditary inclusion body myopathy (IBM) associated with Paget disease of bone (PDB), and frontotemporal dementia (FTD). More recently, these mutations have been linked to 2% of familial amyotrophic lateral sclerosis (ALS) cases. A knock‐in mouse model offers the opportunity to study VCP‐associated pathogenesis.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Methods:</title> <p>The <italic>VCP</italic><sup>R155H/+</sup> knock‐in mouse model was assessed for muscle strength and immunohistochemical, Western blot, apoptosis, autophagy, and microPET/CT imaging analyses.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results:</title> <p> <italic>VCP</italic> <sup>R155H/+</sup> 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.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusions:</title> <p> <italic>VCP</italic> <sup>R155H/+</sup> knock‐in mice represent an excellent preclinical model for understanding VCP‐associated disease mechanisms and future treatments. Muscle Nerve, 2013</p> </sec> </abstract>