| First Author | Kim EY | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 6 | Pages | e20803 |
| PubMed ID | 21677783 | Mgi Jnum | J:174135 |
| Mgi Id | MGI:5051983 | Doi | 10.1371/journal.pone.0020803 |
| Citation | Kim EY, et al. (2011) Expression of sumoylation deficient nkx2.5 mutant in nkx2.5 haploinsufficient mice leads to congenital heart defects. PLoS One 6(6):e20803 |
| abstractText | Nkx2.5 is a cardiac specific homeobox gene critical for normal heart development. We previously identified Nkx2.5 as a target of sumoylation, a posttranslational modification implicated in a variety of cellular activities. Sumoylation enhanced Nkx2.5 activity via covalent attachment to the lysine residue 51, the primary SUMO acceptor site. However, how sumoylation regulates the activity of Nkx2.5 in vivo remains unknown. We generated transgenic mice overexpressing sumoylation deficient mutant K51R (conversion of lysine 51 to arginine) specifically in mouse hearts under the control of cardiac alpha-myosin heavy chain (alpha-MHC) promoter (K51R-Tg). Expression of the Nkx2.5 mutant transgene in the wild type murine hearts did not result in any overt cardiac phenotype. However, in the presence of Nkx2.5 haploinsufficiency, cardiomyocyte-specific expression of the Nkx2.5 K51R mutant led to congenital heart diseases (CHDs), accompanied with decreased cardiomyocyte proliferation. Also, a number of human CHDs-associated Nkx2.5 mutants exhibited aberrant sumoylation. Our work demonstrates that altered sumoylation status may underlie the development of human CHDs associated with Nkx2.5 mutants. |
