Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal. Academic Article uri icon

Overview

abstract

  • Mouse chimeras from embryonic stem cells in which the X-linked glucose 6-phosphate dehydrogenase (G6PD) gene had been targeted were crossed with normal females. First-generation (F(1)) G6PD(+/-) heterozygotes born from this cross were essentially normal; analysis of their tissues demonstrated strong selection for cells with the targeted G6PD allele on the inactive X chromosome. When these F(1) G6PD(+/-) females were bred to normal males, only normal G6PD mice were born, because: (i) hemizygous G6PD(-) male embryos died by E10.5 and their development was arrested from E7.5, the time of onset of blood circulation; (ii) heterozygous G6PD(+/-) females showed abnormalities from E8.5, and died by E11.5; and (iii) severe pathological changes were present in the placenta of both G6PD(-) and G6PD(+/-) embryos. Thus, G6PD is not indispensable for early embryo development; however, severe G6PD deficiency in the extraembryonic tissues (consequent on selective inactivation of the normal paternal G6PD allele) impairs the development of the placenta and causes death of the embryo. Most importantly, G6PD is indispensable for survival when the embryo is exposed to oxygen through its blood supply.

publication date

  • August 15, 2002

Research

keywords

  • Genes, Lethal
  • Glucosephosphate Dehydrogenase
  • Glucosephosphate Dehydrogenase Deficiency

Identity

PubMed Central ID

  • PMC126165

Scopus Document Identifier

  • 18544369618

Digital Object Identifier (DOI)

  • 10.1093/emboj/cdf426

PubMed ID

  • 12169625

Additional Document Info

volume

  • 21

issue

  • 16