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Death of mouse embryos that lack a functional gene for glucose phosphate isomerase

Published online by Cambridge University Press:  14 April 2009

John D. West*
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh, EH3 9EW, UK
Jean H. Flockhart
Affiliation:
Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh, EH3 9EW, UK
Josephine Peters
Affiliation:
MRC Radiobiology Unit, Chilton, Didcot, Oxfordshire, OX11 0RD, UK
Simon T. Ball
Affiliation:
MRC Radiobiology Unit, Chilton, Didcot, Oxfordshire, OX11 0RD, UK
*
* Corresponding author.

Summary

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A null allele of the Gpi-1s structural gene, that encodes glucose phosphate isomerase (GPI-1; E.C. 5.3.1.9), arose in a mutation experiment and was designated Gpi-1sa-m1H. The viability of homozygotes has been investigated. No offspring homozygous for the null allele were produced by intercrossing two heterozygotes, so the homozygous condition was presumed to be embryonic lethal. Embryos were produced by crossing Gpi-1sa/null heterozygous females and Gpi-1sb/null heterozygous males. Homozygous null embryos were identified at different stages of development by electrophoresis and staining either for GPI-1 alone or GPI-1 plus phosphoglycerate kinase (PGK) activity. At 6½ and 7½ days post coitum homozygous null embryos were present at approximately the expected 25% frequency (37/165; 22·4% overall) although at 7½ days the homozygous null embryos tended to be small. By 8½ days most homozygous null embryos were developmentally retarded and had not developed significantly further than at 7½ days; some were dead or dying. By 9½ days the homozygous null conceptus was characterised by a small implantation site that contained trophoblast and often a small amount of extraembryonic membrane. Surviving trophoblast tissue was also detectable at 10½ days. Previous studies have shown that oocyte-coded GPI-1 persists only until 5½ or 6½ days. Survival of homozygous null embryos to 7½ or 8½ days and survival of certain extraembryonic tissue to 10½ days suggests that the homozygous null condition may not be cell-lethal although it is certainly embryo-lethal. Mutant cells that are deficient in glycolysis may use the pentose phosphate shunt to bypass the block in glycolysis created by the deficiency of glucose phosphate isomerase, and/or might be rescued by the transport, from the maternal blood, of energy sources other than glucose (such as glutamine). Either strategy may only permit slow cell growth that would not be adequate to support normal embryogenesis. Transport of maternal nutrients would be more efficient to the trophoblast and extraembryonic membranes and this may help to explain why these tissues survive for longer than the embryo itself. The morphological similarity between homozygous nulls and androgenetic conceptuses, where the trophoblast also survives better than the embryo, is discussed.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1990

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