Disease relevance of Irx4

• In the absence of genes under the control of Irx4, ventricular function deteriorates and cardiomyopathy ensues [1].

High impact information on Irx4

• We conclude that Irx4 is not sufficient for ventricular chamber formation but is required for the establishment of some components of a ventricle-specific gene expression program [1].
• To define the role of Irx4, a member of the Iroquois family of homeobox transcription factors in mammalian heart development and function, we disrupted the murine Irx4 gene [1].
• Cardiac morphology in Irx4-deficient mice (designated Irx4(Delta ex2/Delta ex2)) was normal during embryogenesis and in early postnatal life [1].
• Our molecular analyses also revealed the cooperative regulation of the homeodomain protein, Irx4, by Nkx2.5 and dHAND [2].
• Throughout all subsequent stages in which the chambers of the heart become morphologically distinct (E8.5-11) and into adulthood, cardiac Irx4 expression is found exclusively in the ventricular myocardium [3].

Anatomical context of Irx4

• Irx4 expression was observed in a segment of the linear heart tube and the atrioventricular canal and ventricular myocardium including the inner curvature after looping, resembling the pattern of MLC2V [4].
• In mice at embryonic day (E) 7.5, Irx4 transcripts are found in the chorion and at low levels in a discrete anterior domain of the cardiac primordia [3].
• Irx4 is expressed in a subset of cells in the neural retina and the developing hindbrain and also, specifically, in the ventricle of the heart [5].

Analytical, diagnostic and therapeutic context of Irx4

• All six murine Irx genes are expressed in the developing heart, suggesting that they might possess distinct functions during heart development, and a role for Irx4 in normal heart development has been recently demonstrated by gene-targeting experiments [6].

References