Posted 3 February 2011

General Information

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.

Mutation: R155H

Promoter: N/A

Mouse strain: C57BL/6. 129/SvEv. C57BL/6 origin; Backcross N6. >10 backcrosses.

Phenotype

Neuropathological analysis:

KI mice show increased TDP-43 and ubiquitin-positive inclusions in frontal cortex and express R155H mutant VCP gene at an endogenous level.

Behavioral Phenotype:

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.

Availability

Contact: Virginia E. Kimonis
Department of Pediatrics, University of California Irvine, Irvine, California, Phone: 949-824-0571, Fax: 714-456-5330.

References

Primary:

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. Abstract