Posted 7 December 2010
Human VCP (Valosin-containing protein) cDNA was obtained from Origene. Disease associated
mutations R155H and A232E were introduced using the QuickChange Site-Directed Mutagenesis
Kit (Stratagene) as directed. The cDNA was then subcloned into the SmaI site of
pCX-A. DNA was microinjected into male SJL pronuclei, which were then transferred
to foster females. Positive founders were bred to C57/B6 animals to produce F2 progeny.
Mutation: R155H and A232E.
Mouse strain: SJL. Origin: C57/B6; Background: C57/B6 F2.
Recapitulate spectrum of disease in human inclusion body myopathy with Paget’s frontotemporal
dementia (IBMPFD). Pathological examination of the brain shows widespread TDP-43
The mice exhibit abnormalities in behavioral testing. Progressive muscle weakness.
Severe osteopenia accompanied by focal lytic and sclerotic lesions in vertebrae
and femur. Wt and mutant mice develop normally initially, but both mutants began
to show adult-onset weight loss at ~9 months of age and continued to decline relative
to wt. At 3-6 months some mutant mice show hindlimb clasping phenotype increasing
in severity over time.
Contact: J. Paul Taylor
Developmental Neurobiology, MS 343, D-4026, St. Jude Children’s Research Hospital,
262 Danny Thomas Place, Memphis, TN 38105-, Phone: +90115956047, Fax: +90115952032
Custer SK, Neumann M, Lu H, Wright AC, Taylor JP. Transgenic mice expressing mutant
forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in
muscle, brain and bone. Hum Mol Genetics 2010, 19(9):1741-1755.