NEURAL-TUBE DEFECTS AND ABNORMAL BRAIN-DEVELOPMENT IN F52-DEFICIENT MICE

F52 is a myristoylated, alanine-rich substrate for protein kinase C, W e have generated F52-deficient mice by the gene targeting technique. T hese mutant mice manifest severe neural tube defects that are not asso ciated with other complex malformations, a phenotype reminiscent of co mmon human neural tube defects. The neural tube defects observed inclu de both exencephaly and spina hifida, and the phenotype exhibits parti al penetrance with about 60% of homozygous embryos developing neural t ube defects, Exencephaly is the prominent type of defect and leads to high prenatal lethality, Neural tube defects are observed in a smaller percentage of heterozygous embryos (about 10%). Abnormal brain develo pment and tail formation occur in homozygous mutants and are likely to be secondary to the neural tube defects, Disruption of F52 in mice th erefore identifies a gene whose mutation results in isolated neural tu be defects and may provide an animal model for common human neural tub e defects.