PRENATAL FOLIC-ACID TREATMENT SUPPRESSES ACRANIA AND MEROANENCEPHALY IN MICE MUTANT FOR THE CART1 HOMEOBOX GENE

The paired-class homeobox-containing gene, Cart1, is expressed in fore brain mesenchyme, branchial arches, limb buds and cartilages during em bryogenesis. Here, we show that Cart1-homozygous mutant mice are born alive with acrania and meroanencephaly but die soon after birth - a ph enotype that strikingly resembles a corresponding human syndrome cause d by a neural tube closure defect. Developmental studies suggest that Cart1 is required for forebrain mesenchyme survival and that its absen ce disrupts cranial neural tube morphogenesis by blocking the initiati on of closure in the midbrain region that ultimately leads to the gene ration of lethal craniofacial defects. Prenatal treatment of Cart1 hom ozygous mutants with folic acid suppresses the development of the acra nia/meroanencephaly phenotype.