Dach1 mutant mice bear no gross abnormalities in eye, limb, and brain development and exhibit postnatal lethality

Drosophila dachshund is necessary and sufficient for compound eye developme nt and is required for normal leg and brain development. A mouse homologue of dachshund, Dach1, is expressed in the developing retina and limbs, sugge sting functional conservation of this gene. We have generated a loss-of-fun ction mutation in Dach1 that results in the abrogation of the wild-type RNA and protein expression pattern in embryos. Homozygous mutants survive to b irth but exhibit postnatal lethality associated with a failure to suckle, c yanosis? and respiratory distress. The heart, lungs, kidneys, liver, and sk eleton were examined to identify factors involved in postnatal lethality, h ut these organs appeared to be normal. In addition, blood chemistry tests f ailed to reveal differences that might explain the lethal phenotype. Gross examination and histological analyses of newborn eyes, limbs, and brains re vealed no detectable abnormalities. Since Dach1 mutants die! shortly after birth, it re mains possible that Dach1 is required for postnatal developmen t of these structures.;Alternatively, an additional Dach homologue may func tionally compensate for Dach1 loss of function.