| First Author | Nalbandian A | Year | 2013 |
| Journal | Muscle Nerve | Volume | 47 |
| Issue | 2 | Pages | 260-70 |
| PubMed ID | 23169451 | Mgi Jnum | J:278263 |
| Mgi Id | MGI:6356495 | Doi | 10.1002/mus.23522 |
| Citation | Nalbandian A, et al. (2013) A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H/+) mouse. Muscle Nerve 47(2):260-70 |
| abstractText | INTRODUCTION: Mutations in the valosin-containing protein (VCP) 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. METHODS: The VCP(R155H/+) knock-in mouse model was assessed for muscle strength and immunohistochemical, Western blot, apoptosis, autophagy, and microPET/CT imaging analyses. RESULTS: VCP(R155H/+) 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. CONCLUSIONS: VCP(R155H/+) knock-in mice represent an excellent preclinical model for understanding VCP-associated disease mechanisms and future treatments. |
