The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in Mice

Abstract

The Iroquois homeobox (Irx) genes have been implicated in the specification and patterning of several organs in Drosophila and several vertebrate species. Misexpression studies of chick, Xenopus, and zebra fish embryos have demonstrated that Irx genes are involved in the specification of the midbrain-hindbrain boundary. 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. Here we describe the generation and phenotypic analysis of an Irx2-deficient mouse strain. By targeted insertion of a lacZ reporter gene into the Irx2 locus, we show that lacZ expression reproduces most of the endogenous Irx2 expression pattern. Despite the dynamic expression of Irx2 in the developing heart, nervous system, and other organs, Irx2-deficient mice are viable, are fertile, and appear to be normal. Although chick Irx2 has been implicated in the development of the midbrain-hindbrain region, we show that Irx2-deficient mice develop a normal midbrain-hindbrain boundary. Furthermore, Irx2-deficient mice have normal cardiac morphology and function. Functional compensation by other Irx genes might account for the absence of a phenotype in Irx2-deficient mice. Further studies of mutant mice of other Irx genes as well as compound mutant mice will be necessary to uncover the functional roles of these evolutionarily conserved transcriptional regulators in development and disease.

ACKNOWLEDGMENTS

This research was funded by operating grants from the Canadian Institutes of Health Research (CIHR) to C.-C.H and B.G.B and by a CIHR interdisciplinary group grant to B.G.B. and M.H. The work described in this paper was also partially supported by a grant from the Research Grants Council of the Hong Kong SAR (project no. City U 1164/02 M). M.L. is the recipient of a doctoral award from the Fond de la Recherche en Santé du Québec, P.A. is the recipient of a National Science and Engineering Research Council of Canada Scholarship, T.Y.C was supported by studentships by the Canadian Hypertension Society and Heart and Stroke Foundation of Ontario, M.H. holds a Clinician Scientist Award from CIHR, B.G.B. holds a Canada Research Chair in Developmental Cardiology, and C.-C.H. is a Research Scientist of the National Cancer Institute of Canada.

We thank C. Lobe for the gift of the NLS-Cre mice.