| First Author | Rajan I | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 8 | Pages | e6612 |
| PubMed ID | 19672313 | Mgi Jnum | J:152466 |
| Mgi Id | MGI:4358814 | Doi | 10.1371/journal.pone.0006612 |
| Citation | Rajan I, et al. (2009) Loss of the putative catalytic domain of HDAC4 leads to reduced thermal nociception and seizures while allowing normal none development. PLoS One 4(8):e6612 |
| abstractText | 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 increased latency to respond to a thermal nociceptive stimulus. As the mutant mice aged past 5 months, convulsions appeared, often elicited by handling. Our findings confirm the sufficiency of the N-terminal domain for muscle and bone development, while revealing other roles of HDAC4. |
