Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene

Nat Genet. 1996 Jul;13(3):275-83. doi: 10.1038/ng0796-275.


The paired-class homeobox-containing gene, Cart1, is expressed in forebrain mesenchyme, branchial arches, limb buds and cartilages during embryogenesis. Here, we show that Cart1-homozygous mutant mice are born alive with acrania and meroanencephaly but die soon after birth-a phenotype that strikingly resembles a corresponding human syndrome caused by a neural tube closure defect. Developmental studies suggest that Cart1 is required for forebrain mesenchyme survival and that its absence disrupts cranial neural tube morphogenesis by blocking the initiation of closure in the midbrain region that ultimately leads to the generation of lethal craniofacial defects. Prenatal treatment of Cart1 homozygous mutants with folic acid suppresses the development of the acrania/meroanencephaly phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anencephaly / drug therapy
  • Anencephaly / prevention & control*
  • Animals
  • Apoptosis / drug effects
  • DNA-Binding Proteins / genetics*
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / pharmacology*
  • Homeodomain Proteins
  • Humans
  • Maternal-Fetal Exchange*
  • Mesoderm / cytology
  • Mesoderm / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic / embryology
  • Mutation*
  • Neural Tube Defects / pathology
  • Neural Tube Defects / prevention & control*
  • Pregnancy
  • Prosencephalon / abnormalities
  • Prosencephalon / embryology
  • Prosencephalon / ultrastructure
  • Skull / abnormalities*
  • Skull / embryology


  • ALX1 protein, human
  • Alx1 protein, mouse
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Folic Acid