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

Letizia Longo, Olga Camacho Vanegas, Meghavi Patel, Vittorio Rosti, Haiqing Li, John Waka, Taha Merghoub, Pier Paolo Pandolfi, Rosario Notaro, Katia Manova, Lucio Luzzatto

Research output: Contribution to journalArticle

94 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)4229-4239
Number of pages11
JournalEMBO Journal
Volume21
Issue number16
DOIs
Publication statusPublished - Aug 15 2002

Fingerprint

Glucosephosphate Dehydrogenase Deficiency
Glucosephosphate Dehydrogenase
Embryonic Structures
Placenta
Blood Circulation Time
Alleles
Tissue
X Chromosome
Heterozygote
Hemodynamics
Chromosomes
Stem cells
Embryonic Development
Cause of Death

Keywords

  • G6PD deficiency
  • Hemizygotes
  • Heterozygotes
  • Lethality
  • Oxidative damage

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Longo, L., Vanegas, O. C., Patel, M., Rosti, V., Li, H., Waka, J., ... Luzzatto, L. (2002). Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal. EMBO Journal, 21(16), 4229-4239. https://doi.org/10.1093/emboj/cdf426

Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal. / Longo, Letizia; Vanegas, Olga Camacho; Patel, Meghavi; Rosti, Vittorio; Li, Haiqing; Waka, John; Merghoub, Taha; Pandolfi, Pier Paolo; Notaro, Rosario; Manova, Katia; Luzzatto, Lucio.

In: EMBO Journal, Vol. 21, No. 16, 15.08.2002, p. 4229-4239.

Research output: Contribution to journalArticle

Longo, L, Vanegas, OC, Patel, M, Rosti, V, Li, H, Waka, J, Merghoub, T, Pandolfi, PP, Notaro, R, Manova, K & Luzzatto, L 2002, 'Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal', EMBO Journal, vol. 21, no. 16, pp. 4229-4239. https://doi.org/10.1093/emboj/cdf426
Longo, Letizia ; Vanegas, Olga Camacho ; Patel, Meghavi ; Rosti, Vittorio ; Li, Haiqing ; Waka, John ; Merghoub, Taha ; Pandolfi, Pier Paolo ; Notaro, Rosario ; Manova, Katia ; Luzzatto, Lucio. / Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal. In: EMBO Journal. 2002 ; Vol. 21, No. 16. pp. 4229-4239.
@article{1ecf3d3a255d42e4a6f495d11c3adc47,
title = "Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal",
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 (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",
author = "Letizia Longo and Vanegas, {Olga Camacho} and Meghavi Patel and Vittorio Rosti and Haiqing Li and John Waka and Taha Merghoub and Pandolfi, {Pier Paolo} and Rosario Notaro and Katia Manova and Lucio Luzzatto",
year = "2002",
month = "8",
day = "15",
doi = "10.1093/emboj/cdf426",
language = "English",
volume = "21",
pages = "4229--4239",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "16",

}

TY - JOUR

T1 - Maternally transmitted severe glucose 6-phosphate dehydrogenase deficiency is an embryonic lethal

AU - Longo, Letizia

AU - Vanegas, Olga Camacho

AU - Patel, Meghavi

AU - Rosti, Vittorio

AU - Li, Haiqing

AU - Waka, John

AU - Merghoub, Taha

AU - Pandolfi, Pier Paolo

AU - Notaro, Rosario

AU - Manova, Katia

AU - Luzzatto, Lucio

PY - 2002/8/15

Y1 - 2002/8/15

N2 - 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.

AB - 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.

KW - G6PD deficiency

KW - Hemizygotes

KW - Heterozygotes

KW - Lethality

KW - Oxidative damage

UR - http://www.scopus.com/inward/record.url?scp=18544369618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18544369618&partnerID=8YFLogxK

U2 - 10.1093/emboj/cdf426

DO - 10.1093/emboj/cdf426

M3 - Article

C2 - 12169625

AN - SCOPUS:18544369618

VL - 21

SP - 4229

EP - 4239

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 16

ER -