Efficient cre-mediated deletion in cardiac progenitor cells conferred by a 3 &#39; UTR-ires-Cre allele of the homeobox gene Nkx2-5

Stanley, EG; Biben, C; Elefanty, A; Barnett, L; Koentgen, F; Robb, L; Harvey, RP

Efficient cre-mediated deletion in cardiac progenitor cells conferred by a 3 ' UTR-ires-Cre allele of the homeobox gene Nkx2-5

Author(s): Stanley, EG; Biben, C; Elefanty, A; Barnett, L; Koentgen, F; Robb, L; Harvey, RP;
Details: Publication Year 2002-01-01,Volume 46,Issue #4,Page 431-439
Journal Title: INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
Publication Type: Journal Article
Abstract: 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. Nkx2-5(IRESCre) mice were fully viable as homozygotes. We evaluated the efficacy of Cre-mediated deletion by crossing Nkx2-5(IRESCre) 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 Nkx2-5(IRESCre) 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.
Publisher: U B C PRESS
Keywords: EMBRYONIC STEM-CELLS; HEART DEVELOPMENT; TRANSGENIC MICE; EXPRESSION; RECOMBINATION; MOUSE; REPORTER; PROTEIN; CARDIOGENESIS; MYOCARDIUM
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Creation Date: 2002-01-01 12:00:00