A new pyruvate kinase mutation with hyperactivity in the mouse

Abstract

A mouse mutant with pyruvate kinase (PK) hyperactivity has been found in offspring of 1-ethyl-1-nitrosourea (ENU)-treated male mice. The activity alteration was detected in the blood and could also be found in the liver but not in the muscle, kidney, heart, spleen, lung, or brain. Heterozygous mice have erythrocyte PK activity enhanced up to about 160% and homozygotes up to about 240%, compared to homozygous wild types. The mutation is codominantly expressed. The heterozygous and homozygous mutants are viable and fully fertile and do not show symptoms of erythrocytosis. The mutation does not affect the heat stability, the electrophoretic mobility, or the Km (for phosphoenolpyruvate) of the PK molecule. It is suggested that the regulatory locus of PK-1 is affected by this mutation. The observations support also the theory of one structural locus for the erythrocyte and liver isozymes.