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

Authors: Rajan, I  Savelieva, KV  Ye, GL  Wang, CY  Malbari, MM  Friddle, C  Lanthorn, TH  Zhang, W 
Citation: Rajan I, etal., PLoS One. 2009 Aug 12;4(8):e6612. doi: 10.1371/journal.pone.0006612.
Pubmed: (View Article at PubMed) PMID:19672313
DOI: Full-text: DOI:10.1371/journal.pone.0006612

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.


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RGD Object Information
RGD ID: 9681457
Created: 2014-12-02
Species: All species
Last Modified: 2014-12-02
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.