First Author | Nozaki M | Year | 1999 |
Journal | Lab Invest | Volume | 79 |
Issue | 3 | Pages | 293-9 |
PubMed ID | 10092065 | Mgi Jnum | J:53967 |
Mgi Id | MGI:1333692 | Citation | Nozaki M, et al. (1999) Developmental abnormalities of glycosylphosphatidylinositol-anchor-deficient embryos revealed by Cre/loxP system. Lab Invest 79(3):293-9 |
abstractText | One mode used to link membrane proteins to a cell membrane is by means of a special glycolipid anchor termed glycosylphosphatidylinositol (GPI). Pig-a, an X-linked gene, is involved in the first step of GPI- anchor biosynthesis. Disruption of this gene causes cessation of GPI biosynthesis on the endoplasmic reticulum, thereby leading to the absence of GPI-anchored proteins on the cell surface. We have previously reported that mice with high chimerism was never obtained from Pig-a disrupted ES cells, suggesting that GPI-anchored protein(s) may have important roles for mouse development such that the absence of GPI-anchored proteins causes a lethal effect to mice. In this study, this lethal effect has been investigated by using a conditional approach to knockout the Pig-a gene. For this, mice harboring a Pig-a gene flanked by two loxP sites (Pig-aflox) were mated with hCMV-Cre transgenic mice, which express Cre recombinase before implantation. The allele disruptions were identified by PCR analysis of embryo yolk sac DNA. Embryos harboring a complete disruption of Pig-a gene ceased to develop beyond the ninth day of gestation. Female embryos in which one Pig-a allele was disrupted by Cre such that only half of the cells in the embryo proper did not express GPI-anchored proteins due to random X inactivation developed until 19 days post coitum (dpc), but showed abnormal phenotypes such as insufficient closure of neural tube and cleft palate. These data further highlight the importance of GPI- anchored proteins during mouse embryonic development. |