Posted 3 February 2011
Mouse genomic VCP fragment with 7.9 kb of upstream homology seq. and 2.1 kb of downstream
homology seq. was subcloned into a targeting vector. Site-directed mutagenesis was
used to introduce the R to H mutation at aa position 155 and targeting vector was
linearized by NotI then electroporated into 129/SvEv mice.
Mouse strain: C57BL/6. 129/SvEv. C57BL/6 origin; Backcross N6. >10 backcrosses.
KI mice show increased TDP-43 and ubiquitin-positive inclusions in frontal cortex
and express R155H mutant VCP gene at an endogenous level.
Demonstrate progressive muscle weakness (6 months). Spontaneous seizures seen in
12.3% mice. Mice exhibit muscle weakness, vacuoles and inclusions in the muscle
fibers, Paget like bone changes and typical brain pathology of IBMPFD.
Contact: Virginia E. Kimonis
Department of Pediatrics, University of California Irvine, Irvine, California, Phone:
949-824-0571, Fax: 714-456-5330.
Badadani M, Nalbandian A, Watts GD, Vesa J, Kitazawa M , Su H, Tanaja J, Dec E,
Wallace DC, Mukherjee J, Caiozzo V, Warman M, Kimonis VE. VCP Associated Inclusion
Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology
Typical of Human Disease. Plos One 2010 5(10): 13183.