| Autor: |
Nalbandian, A, Llewellyn, KJ, Badadani, M, Yin, HZ, Nguyen, C, Katheria, V, Watts, G, Mukherjee, J, Vesa, J, Caiozzo, V, Mozaffar, T, Weiss, JH, Kimonis, VE |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Zdroj: |
Nalbandian, A; Llewellyn, KJ; Badadani, M; Yin, HZ; Nguyen, C; Katheria, V; et al.(2013). A progressive translational mouse model of human valosin-containing protein disease: The VCPR155H/+mouse. Muscle and Nerve, 47(2), 260-270. doi: 10.1002/mus.23522. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/6fv693w5 |
| DOI: |
10.1002/mus.23522. |
| Popis: |
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 VCPR155H/+knock-in mouse model was assessed for muscle strength and immunohistochemical, Western blot, apoptosis, autophagy, and microPET/CT imaging analyses. Results: 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. Conclusions: VCPR155H/+knock-in mice represent an excellent preclinical model for understanding VCP-associated disease mechanisms and future treatments. © 2012 Wiley Periodicals, Inc. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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