Jumonji, a nuclear protein that is necessary for normal heart development

Jumonji (jmj) was cloned in a gene trap screen to identify and mutagenize g enes important for heart development, To investigate the role of jmj in hea rt development, we generated mice homozygous for the jmj mutation. The jmj homozygous mouse embryos showed heart malformations, including ventricular septal defect, noncompaction of the ventricular wall, double-outlet right v entricle, and dilated atria. The jmj mutants died soon after birth, apparen tly as a result of respiratory insufficiency caused by rib and sternum defe cts in addition to the heart defects. In situ hybridization analyses sugges ted that cardiomyocytes were differentiated but developmental regulation of chamber-specific genes was defective in fetal hearts. Expression of jmj wa s detected in the myocardium, especially in the interventricular septum, ve ntricular wall, and outflow tract, which correlated well with the locations of defects observed in the hearts of mutant mice, Homozygous embryos faile d to express the jmj transcript in all tissues except in the nervous system . Confocal microscopic examination using anti-JMJ antibodies indicated that the JMJ protein was localized in the nuclei of cells transfected with jmj. These data demonstrate that JMJ is a nuclear protein, which is essential f or normal heart development and function.