A glucosephosphate isomerase (GPI) null mutation in Mus musculus: evidence that anaerobic glycolysis is the predominant energy delivering pathway in early post-implantation embryos

Abstract

1. A heterozygous mouse mutant exhibiting approximately 50% of wild-type glucose-6-phosphate isomerase (GPI) activity in blood was recovered in mutagenicity experiments after combined treatment of spermatogonia with triethylenemelamine and irradiation. 2. Biochemical and immunological studies revealed no differences in physicochemical, kinetic and immunological properties between the erythrocytic enzyme of heterozygous and wild-type animals. This suggests that the mutation generates a null allele at the Gpi-1s structural locus, producing neither enzyme activity nor immunologically detectable material. 3. In accordance with the presence of only one functional Gpi-1s gene per haploid genome in the mouse, the 50% deficiency in heterozygotes is expressed in plasma and all tissues studied. 4. The genetic and physiological analyses provided no indications for further altered traits in heterozygous animals including fertility, viability and several other traits. 5. Homozygous mutants died at an early post-implantation stage of embryogenesis. 6. These findings support the hypothesis that a mutation resulting in a total loss of catalytic activity of a glycolytic enzyme leads to lethality of homozygous carriers at an early post-implantation stage of embryonic development due to a block of glycolysis and the resulting inability to utilize glucose as a source of metabolic energy. Furthermore, they indicate that anaerobic glycolysis primarily supplies the metabolic energy used by early post-implantation mouse embryos.