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  • The EMBO Journal (2002) 21, 4229 - 4239
  • doi:10.1093/emboj/cdf426

Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal

Letizia Longo1, Olga Camacho Vanegas1,2, Meghavi Patel3, Vittorio Rosti1,4, Haiqing Li1,5, John Waka3, Taha Merghoub1,6, Pier Paolo Pandolfi1,6, Rosario Notaro7, Katia Manova3 and Lucio Luzzatto1,5,7

  1. Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
  2. Present address: Department of Human Genetics, Mount Sinai School of Medicine, Madison Avenue, New York, NY 10029, USA
  3. Molecular Cytology Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
  4. Present address: Dipartimento Medicina Interna e Terapia Medica, IRCCS Policlinico San Matteo, Piazzale Golgi 2, I-27100 Pavia, Italy
  5. Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
  6. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
  7. IST, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, I-16132 Genova, Italy

Correspondence to:

Lucio Luzzatto, E-mail: lucio.luzzatto@istge.it

Received 21 February 2002; Accepted 1 July 2002; Revised 26 April 2002

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 (F1) 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 F1 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.

  • Keywords:

    • G6PD deficiency,
    • hemizygotes,
    • heterozygotes,
    • lethality,
    • oxidative damage