Targeted excision of VCP R155H mutation by Cre-LoxP technology as a promising therapeutic strategy for valosin-containing protein disease.

ABSTRACT: Inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia is attributed to mutations in the valosin-containing protein (VCP) gene, mapped to chromosomal region 9p13.3-12. Affected individuals exhibit scapular winging and die from progressive muscle weakness and cardiac and respiratory failure in their 40s to 50s. Mutations in the VCP gene have also been associated with amyotrophic lateral sclerosis in 10-15% of individuals with hereditary inclusion body myopathy and 2-3% of isolated familial amyotrophic lateral sclerosis. Currently, there are no effective treatments for VCP-related myopathy or dementia. To determine the effects of targeted excision of the most common R155H mutation in VCP disease, we generated the Cre-ER™-VCPR155H/+ tamoxifen-inducible

SUBMITTER: Nalbandian A 

PROVIDER: S-EPMC4337464 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature