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Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart 总被引:9,自引:0,他引:9
Toko H Zhu W Takimoto E Shiojima I Hiroi Y Zou Y Oka T Akazawa H Mizukami M Sakamoto M Terasaki F Kitaura Y Takano H Nagai T Nagai R Komuro I 《The Journal of biological chemistry》2002,277(27):24735-24743
Csx/Nkx2-5, which is essential for cardiac development of the embryo, is abundantly expressed in the adult heart. We here examined the role of Csx/Nkx2-5 in the adult heart using two kinds of transgenic mice. Transgenic mice that overexpress a dominant negative mutant of Csx/Nkx2-5 (DN-TG mice) showed degeneration of cardiac myocytes and impairment of cardiac function. Doxorubicin induced more marked cardiac dysfunction in DN-TG mice and less in transgenic mice that overexpress wild type Csx/Nkx2-5 (WT-TG mice) compared with non-transgenic mice. Doxorubicin induced cardiomyocyte apoptosis, and the number of apoptotic cardiomyocytes was high in the order of DN-TG mice, non-transgenic mice, and WT-TG mice. Overexpression of the dominant negative mutant of Csx/Nkx2-5 induced apoptosis in cultured cardiomyocytes, while expression of wild type Csx/Nkx2-5 protected cardiomyocytes from doxorubicin-induced apoptotic death. These results suggest that Csx/Nkx2-5 plays a critical role in maintaining highly differentiated cardiac phenotype and in protecting the heart from stresses including doxorubicin. 相似文献
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Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development 总被引:9,自引:0,他引:9
Takeuchi JK Mileikovskaia M Koshiba-Takeuchi K Heidt AB Mori AD Arruda EP Gertsenstein M Georges R Davidson L Mo R Hui CC Henkelman RM Nemer M Black BL Nagy A Bruneau BG 《Development (Cambridge, England)》2005,132(10):2463-2474
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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 总被引:14,自引:9,他引:5
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Youngsook Lee Tetsuo Shioi Hideko Kasahara Shawn M. Jobe Russell J. Wiese Bruce E. Markham Seigo Izumo 《Molecular and cellular biology》1998,18(6):3120-3129
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GATA4 is a dosage-sensitive regulator of cardiac morphogenesis 总被引:15,自引:0,他引:15
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Stanley EG Biben C Elefanty A Barnett L Koentgen F Robb L Harvey RP 《The International journal of developmental biology》2002,46(4):431-439
Conditional gene targeting and transgenic strategies utilizing Cre recombinase have been successfully applied to the analysis of development in mouse embryos. To create a conditional system applicable to heart progenitor cells, a Cre recombinase gene linked at its 5' end to an internal ribosome entry site (IRES) was inserted into the 3' untranslated region of the cardiac homeobox gene Nkx2-5 using gene targeting. Nkx2-5IRESCre mice were fully viable as homozygotes. We evaluated the efficacy of Cre-mediated deletion by crossing Nkx2-5IRESCre mice with the Cre-dependent R26R and Z/AP reporter strains. Efficient deletion was observed in the cardiac crescent and heart tube in both strains. However, the Z/AP locus showed transient resistance to deletion in caudal heart progenitors. Such resistance was not evident at the R26R locus, suggesting that Cre-mediated deletion in myocardium may be locus-dependent. From cardiac crescent stages, deletion was seen not only in myocardium, but also endocardium, dorsal mesocardium and pericardial mesoderm. The Cre domain apparently includes cells dorsal to the heart that have been shown to constitute a secondary heart field, contributing myocardium to the outflow tract. Other sites of Nkx2-5 expression, including pharyngeal endoderm and its derivatives, branchial arch epithelium, stomach, spleen, pancreas and liver, also showed efficient deletion. Our data suggest that the Nkx2-5IRESCre strain will be useful for genetic dissection of the multiple tiers of lineage allocation to the forming heart as well as of molecular interactions within the heart fields and heart tube. 相似文献
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