Maternally Transmitted Severe Glucose 6-phosphate Dehydrogenase Deficiency is an Embryonic Lethal

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Aug 10

PMID 12169625

Citations 60

Authors

Letizia Longo

Olga Camacho Vanegas

Meghavi Patel

Vittorio Rosti

Haiqing Li

John Waka

Taha Merghoub

Pier Paolo Pandolfi

Rosario Notaro

Katia Manova

Lucio Luzzatto

Affiliations

Soon will be listed here.

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.

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