Targeted Inactivation of Serum Response Factor in the Developing Heart Results in Myocardial Defects and Embryonic Lethality

• DOI: 10.1128/mcb.24.12.5281-5289.2004
• Publication Date: 2004-05-28T19:52:58Z
• Authors: Ara Parlakian; David Tuil; Ghislaine Hamard; Geneviève Tavernier; Daniele Hentzen; Jean-Paul Concordet; Denise Paulin; Zhenlin Li; Dominique Daegelen
• Keywords: Myocardin; GATA4; Heart development; Embryonic heart; TBX1

Serum response factor (SRF) is at the confluence of multiple signaling pathways controlling transcription immediate-early genes and muscle-specific genes. There are active SRF target sequences in more than 50 expressed three muscle lineages including normal diseased hearts. However, role heart formation has not been addressed vivo thus far due to early requirement for mesoderm formation. We have generated a conditional mutant by using Cre-LoxP strategy that will be extremely useful study embryonic postnatal cardiac functions, as well other tissues. This report shows heart-specific deletion embryo new beta MHC-Cre transgenic mouse line results lethal defects between day 10.5 (E10.5) E13.5, evidenced abnormally thin myocardium, dilated chambers, poor trabeculation, disorganized interventricular septum. At E9.5, we found marked reduction expression essential regulators development, Nkx2.5, GATA4, myocardin, gene c-fos prior overt maldevelopment. conclude crucial differentiation maturation, acting global regulator developmental