Loss of the putative catalytic domain of HDAC4 leads to reduced thermal nociception and seizures while allowing normal bone development.

ABSTRACT: Histone deacetylase 4 (HDAC4) has been associated with muscle & bone development [1]-[6]. N-terminal MEF2 and RUNX2 binding domains of HDAC4 have been shown to mediate these effects in vitro. A complete gene knockout has been reported to result in premature ossification and associated defects resulting in postnatal lethality [6]. We report a viral insertion mutation that deletes the putative deacetylase domain, while preserving the N-terminal portion of the protein. Western blot and immuno-precipitation analysis confirm expression of truncated HDAC4 containing N-terminal amino acids 1-747. These mutant mice are viable, living to at least one year of age with no gross defects in muscle or bone. At 2-4 months of age no behavioral or physiological abnormalities were detected except for an inc

SUBMITTER: Rajan I 

PROVIDER: S-EPMC2720538 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature