The Iroquois homeobox gene Irx2 is not essential for normal development of the heart and midbrain-hindbrain boundary in mice.
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.
Program in Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Mélanie
M
Lebel
Pooja
P
Agarwal
Chi Wa
CW
Cheng
M Golam
MG
Kabir
Toby Y
TY
Chan
Vijitha
V
Thanabalasingham
Xiaoyun
X
Zhang
Dana R
DR
Cohen
Mansoor
M
Husain
Shuk Han
SH
Cheng
Benoit G
BG
Bruneau
Chi-Chung
CC
Hui
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D007763:Lac Operon; D008297:Male; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018398:Homeodomain Proteins; C501596:Irx2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA