Genetic regulation of glucose phosphate isomerase in mouse oocytes

Abstract

THE enzyme glucose phosphate isomerase (GPI; D-glucose-6-phosphate-ketol isomerase EC 5.3.1.9.) catalyses the interconversion of fructose-6-phosphate and glucose-6-phosphate. In mice, the product of the GPI structural gene is a monomer and the enzymatically active dimer results from monomer aggregation^1,2. In inbred strains, GPI is found in either of two electrophoretically distinct forms: GPI-1AA or GPI-1BB (ref. 2). Theoretically, the random association of equal numbers of A and B monomers will result in dimers in the proportion of 25%AA:50%AB:25%BB, and indeed an activity distribution of these proportions is observed when samples of purified AA and BB forms, equal in enzymatic activity are dissociated and reassociated in vitro³. It follows, then, that (1) monomer aggregation is a random process which does not distinguish the monomer types; (2) the electrophoretic forms of GPI are similar enzymatically; (3) the measured activity is linearly proportional to the amount of enzyme. Therefore, the 25%AA:50%AB:25%BB activity distribution of GPI found in the mature tissues of heterozygous mice (Gpi-1^a/b) (ref. 4) indicates that the a and b alleles are equally expressed. However, we show here that this is not the rule for unfertilised ova, for we have observed differences in the expression of GPI in unfertilised ova from the inbred mouse strains DBA/2J, LP/J and C57BL/6J. Mature somatic tissues do not reveal these interstrain differences. We postulate that the amount of GPI in ova is controlled by a cis-active regulator gene linked to the GPI structural locus. This is apparently the first characterisation of a genetic variation affecting the amount of an enzyme in the mouse ovum and it provides a unique opportunity for further exploration of gene regulation during mammalian development.