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Glucose Phosphate Isomerase Enzyme-Activity Mutants in Mus musculus: Genetical and Biochemical Characterization.

Biochem. Genet. 28, 97-110 (1989)
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Two glucose-6-phosphate isomerase (GPI) mutants with approximately 60% residual activity in blood compared to wild type have been independently detected in offspring derived from 1-ethyl-1-nitrosourea-treated male mice. Homozygous mutants with about 20% residual activity were recovered in progeny of inter se matings of heterozygotes. However, in both mutant lines the number of homozygous mutants was less than expected suggesting an increased lethality of these animals. Results of linkage studies and of investigations of physicochemical properties of the mutant enzymes indicate point mutations at theGpi-1s structural locus on chromosome 7. Based on these findings the two new alleles were designatedGpi-1s b-m1Neu andGpi-1s b-m2Neu, respectively. The b-m1Neu allele codes for an erythrocyte enzyme which, in the homodimeric form, exhibits a decreased stability toward heat and urea, an altered isoelectric point, normalpH dependence, an increasedK m for fructose-6-phosphate, and increasedK i's for 6-phosphogluconate and 2,3-diphosphoglycerate (2,3-DPG) compared to the wild-type enzyme. The GPI-1sb-m2Neu homodimer, in contrast, is characterized by an even stronger instability, slightly alteredpH dependence, an increasedK i for 2,3-DPG, normal other kinetics, and normal isoelectric point. The different degree of stability of the mutant homodimersin vitro seems to be reflected in a different degree of stabilityin vivo, since GPI deficiency in general is more strongly expressed in the tissues of the homozygousGpi-1s b-m2Neu mutant compared to the homozygousGpi-1s b-m1Neu mutant. The similarity of the mutant enzymes to the allozymes found in human GPI deficiencies indicates the GPI deficient mouse mutants to be excellent models for the human disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter glucose-6-phosphate isomerase; enzyme-activity mutant; erythrocyte; mouse; structural characteristics
ISSN (print) / ISBN 0006-2928
e-ISSN 1573-4927
Zeitschrift Biochemical Genetics
Quellenangaben Band: 28, Heft: 1, Seiten: 97-110 Artikelnummer: , Supplement: ,
Verlag Springer
Begutachtungsstatus Peer reviewed