Conventional/conditional knockout mice

Ichiro Miyoshi, Tadashi Okamura, Noriyuki Kasai, Tetsuyuki Kitmoto, Shinichi Ichikawa, Soh Osuka, Yoshio Hirabayashi

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Genetically modified mice, created using transgenic technologies and gene targeting, are essential tools for clinical and fundamental research. In sphinoglipid research this became possible when the genes encoding enzymes in the sphingolipid metabolism pathway were identified and cloned. Using these mouse models, we can study the functions of sphingolipids in vivo. However, some of these knockout (KO) strains die in early developmental stages. This indicates that the enzymes and their products, sphingolipids, play a vital role during development. Conditional targeting, using the Cre-loxP system, avoids fetal lethality via a tissue-specific disruption of an allele. Alternatively, introducing tissue-specific transgenes encoding an enzyme with similar activity to that of the disrupted gene prevents embryonic lethality in KO mice. We established gene-modified mice deficient in ceramide glucosyltransferase or serine palmitoyltransferase to gain new insights into the roles of sphingolipids in vivo. These are the enzymes that take the first committed steps in sphingolipid synthesis, which includes the synthesis of ceramide, glycosphingolipid, and sphingomyelin. We found that sphingolipids are essential not only for early embryo development, but also for the formation and maintenance of certain organs.

Original languageEnglish
Title of host publicationSphingolipid Biology
PublisherSpringer Japan
Pages443-451
Number of pages9
ISBN (Print)4431341986, 9784431341987
DOIs
Publication statusPublished - 2006

Keywords

  • ceramide glucosyltransferase
  • conditional knockout
  • gene-modified mice
  • serine palmitoyltransferase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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