Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1 c) from wild mice

We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1 ^c ) in a population of wild mice. The Gpi-1 ^c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1 ^a or Gpi-1 ^b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1 ^c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal K _m 's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1 ^c show only mild hematological symptoms. The frequency of Gpi-1 ^c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1 ^d is reported.This work was supported by M.R.C. grants to Professor R. J. Berry and Dr. H. Kacser, whom we should also like to thank for much help and useful discussion.