Wu M, Chen D F, Sasaoka T, Tonegawa S
Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2110-5. doi: 10.1073/pnas.93.5.2110.
F52 is a myristoylated, alanine-rich substrate for protein kinase C. We have generated F52-deficient mice by the gene targeting technique. These mutant mice manifest severe neural tube defects that are not associated with other complex malformations, a phenotype reminiscent of common human neural tube defects. The neural tube defects observed include both exencephaly and spina bifida, and the phenotype exhibits partial penetrance with about 60% of homozygous embryos developing neural tube 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 development and tail formation occur in homozygous mutants and are likely to be secondary to the neural tube defects. Disruption of F52 in mice therefore identifies a gene whose mutation results in isolated neural tube defects and may provide an animal model for common human neural tube defects.
F52是蛋白激酶C的一种肉豆蔻酰化、富含丙氨酸的底物。我们通过基因靶向技术培育出了F52基因缺陷小鼠。这些突变小鼠表现出严重的神经管缺陷，且与其他复杂畸形无关，这种表型让人联想到常见的人类神经管缺陷。观察到的神经管缺陷包括无脑畸形和脊柱裂，该表型具有部分外显率，约60%的纯合胚胎会出现神经管缺陷。无脑畸形是主要的缺陷类型，导致较高的产前致死率。在较小比例的杂合胚胎（约10%）中也观察到神经管缺陷。纯合突变体中出现异常的脑发育和尾部形成，可能继发于神经管缺陷。因此，小鼠中F52基因的破坏确定了一个其突变导致孤立性神经管缺陷的基因，并可能为常见的人类神经管缺陷提供一个动物模型。
