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(Circulation Research. 2000;86:932.)
© 2000 American Heart Association, Inc.

Molecular Medicine

Jumonji, a Nuclear Protein That Is Necessary for Normal Heart Development

Youngsook Lee, Alice J. Song, Robert Baker, Bruce Micales, Simon J. Conway, Gary E. Lyons

From the Cardiovascular Research Center and Department of Anatomy (Y.L., A.J.S., R.B., B.M., G.E.L.), University of Wisconsin Medical School, Madison, Wis, and Institute of Molecular Medicine and Genetics, Department of Cell Biology and Anatomy (S.J.C.), Medical College of Georgia, Augusta, Ga. Present address of R.B. is Department of Nutritional Sciences, University of Arizona, Tucson, Ariz.

Correspondence to Gary E. Lyons, PhD, Department of Anatomy, University of Wisconsin Medical School, 1300 University Ave, Madison, WI 53706. E-mail gelyons{at}facstaff.wisc.edu

Abstract—Jumonji (jmj) was cloned in a gene trap screen to identify and mutagenize genes important for heart development. To investigate the role of jmj in heart 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 ventricle, and dilated atria. The jmj mutants died soon after birth, apparently as a result of respiratory insufficiency caused by rib and sternum defects in addition to the heart defects. In situ hybridization analyses suggested that cardiomyocytes were differentiated but developmental regulation of chamber-specific genes was defective in fetal hearts. Expression of jmj was detected in the myocardium, especially in the interventricular septum, ventricular wall, and outflow tract, which correlated well with the locations of defects observed in the hearts of mutant mice. Homozygous embryos failed 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 for normal heart development and function.

Key Words: jumonji • cardiac abnormalities • gene trap

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