RESUMEN
jumonji (jmj) mutant mice, obtained by a gene trap strategy, showed several morphological abnormalities including neural tube and cardiac defects, and died in utero around embryonic day 11.5 (E11.5). It is unknown what causes the embryonic lethality. Here, we demonstrate that exogenous expression of jmj gene in the heart of jmj mutant mice rescued the morphological phenotypes in the heart, and these embryos survived until E13.5. These results suggest that there are at least two lethal periods in jmj mutant mice, and that cardiac abnormalities may cause the earlier lethality. In addition, the rescue of the cardiac abnormalities by the jmj transgene provided solid evidence that the cardiac abnormalities resulted from mutation of the jmj gene.
Asunto(s)
Cardiopatías Congénitas/etiología , Proteínas del Tejido Nervioso/genética , Animales , Embrión de Mamíferos/patología , Genes Letales , Cardiopatías Congénitas/metabolismo , Cardiopatías Congénitas/patología , Ratones , Ratones Mutantes , Ratones Transgénicos , Miocardio/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Complejo Represivo Polycomb 2RESUMEN
Spatiotemporal regulation of cell proliferation is necessary for normal tissue development. The molecular mechanisms, especially the signaling pathways controlling the cell cycle machinery, remain largely unknown. Here, we demonstrate a negative relationship between the spatiotemporal patterns of jumonji (jmj) expression and cardiac myocyte proliferation. cyclin D1 expression and cell proliferation are enhanced in the cardiac myocytes of jmj-deficient mutant embryos. In contrast, jmj overexpression represses cyclin D1 expression in cardiac cells, and Jmj protein binds to cyclin D1 promoter in vivo and represses its transcriptional activity. cyclin D1 overexpression causes hyperproliferation in the cardiac myocytes, but the absence of cyclin D1 in jmj mutant embryos rescues the hyperproliferation. Therefore, Jmj might control cardiac myocyte proliferation and consequently cardiac morphogenesis by repressing cyclin D1 expression.