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

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.

[1]  T. Takeuchi,et al.  jumonji gene is essential for the neurulation and cardiac development of mouse embryos with a C3H/He background , 1999, Mechanisms of Development.

[2]  D. Srivastava,et al.  A molecular pathway revealing a genetic basis for human cardiac and craniofacial defects. , 1999, Science.

[3]  A. Miyajima,et al.  Definitive but not primitive hematopoiesis is impaired in jumonji mutant mice. , 1999, Blood.

[4]  J. Seidman,et al.  Congenital heart disease caused by mutations in the transcription factor NKX2-5. , 1998, Science.

[5]  P. Gruss,et al.  Efficiency assessment of the gene trap approach , 1998, Developmental dynamics : an official publication of the American Association of Anatomists.

[6]  G. Pall,et al.  Gene trap integrations expressed in the developing heart: Insertion site affects splicing of the PT1‐ATG vector , 1998, Developmental dynamics : an official publication of the American Association of Anatomists.

[7]  Youngsook Lee,et al.  The Cardiac Tissue-Restricted Homeobox Protein Csx/Nkx2.5 Physically Associates with the Zinc Finger Protein GATA4 and Cooperatively Activates Atrial Natriuretic Factor Gene Expression , 1998, Molecular and Cellular Biology.

[8]  K. Chien,et al.  Ventricular muscle-restricted targeting of the RXRalpha gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis. , 1998, Development.

[9]  M. Fishman,et al.  Parsing the Heart: Genetic Modules for Organ Assembly , 1997, Cell.

[10]  T. Takeuchi,et al.  Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice , 1997, Mechanisms of Development.

[11]  G. Boivin,et al.  TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. , 1997, Development.

[12]  C. Bucana,et al.  Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. , 1997, Science.

[13]  G. Lyons,et al.  In vitro preselection of gene-trapped embryonic stem cell clones for characterizing novel developmentally regulated genes in the mouse. , 1997, Developmental biology.

[14]  B. Nadal-Ginard,et al.  Myocyte-specific enhancer factor 2 and thyroid hormone receptor associate and synergistically activate the alpha-cardiac myosin heavy-chain gene , 1997, Molecular and cellular biology.

[15]  E. Olson,et al.  Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. , 1997, Genes & development.

[16]  K Sigrist,et al.  GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. , 1997, Genes & development.

[17]  R E Poelmann,et al.  Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo. , 1997, Circulation research.

[18]  G. Boivin,et al.  TGF β 2 knockout mice have multiple developmental defects that are non-overlapping with other TGF β knockout phenotypes , 1997 .

[19]  G. Lyons,et al.  Vertebrate heart development. , 1996, Current opinion in genetics & development.

[20]  B. Wold,et al.  Know Your Neighbors: Three Phenotypes in Null Mutants of the Myogenic bHLH Gene MRF4 , 1996, Cell.

[21]  R. Saint,et al.  Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins , 1996, Molecular and cellular biology.

[22]  R. Scheuermann,et al.  The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family. , 1995, Genes & development.

[23]  E. Wagner,et al.  Strain-dependent epithelial defects in mice lacking the EGF receptor. , 1995, Science.

[24]  Ruili Li,et al.  Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. , 1995, Genes & development.

[25]  T. Takeuchi,et al.  Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. , 1995, Genes & development.

[26]  N. Copeland,et al.  Retroviral sequences located within an intron of the dilute gene alter dilute expression in a tissue‐specific manner. , 1995, The EMBO journal.

[27]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. , 1994, Development.

[28]  R. Evans,et al.  RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. , 1994, Genes & development.

[29]  G. Lyons.  In situ analysis of the cardiac muscle gene program during embryogenesis. , 1994, Trends in cardiovascular medicine.

[30]  J. Drouin,et al.  Developmental stage-specific regulation of atrial natriuretic factor gene transcription in cardiac cells , 1994, Molecular and cellular biology.

[31]  K. Helin,et al.  Characterization of the retinoblastoma binding proteins RBP1 and RBP2. , 1993, Oncogene.

[32]  M. Ewen,et al.  Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. , 1993, Genes & development.

[33]  I. Herskowitz,et al.  Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription , 1992, Cell.

[34]  Matthew H. Kaufman,et al.  The Atlas of Mouse Development , 1992 .

[35]  G. Lyons,et al.  Developmental regulation of myosin gene expression in mouse cardiac muscle , 1990, The Journal of cell biology.

[36]  P. Cummins.  Transitions in human atrial and ventricular myosin light-chain isoenzymes in response to cardiac-pressure-overload-induced hypertrophy. , 1982, The Biochemical journal.