PYRUVATE-KINASE DEFICIENCY OF MICE ASSOCIATED WITH NONSPHEROCYTIC HEMOLYTIC-ANEMIA AND CURE OF THE ANEMIA BY MARROW TRANSPLANTATION WITHOUTHOST IRRADIATION

Mutant mice with splenomegaly and nonspherocytic hemolytic anemia were found in an inbred colony of the CBA/N (hereafter CBA) strain maintai ned in the Japan SLC Haruno farm (Shuchi-gun, Shizuoka, Japan). The ac tivity of pyruvate kinase (PK) in red blood cells (RBCs) of the anemic mutants decreased to 16.2% of normal (+/+) CBA mice. Because the muta nt CBA mice showed a remarkable reticulocytosis (41.6%) and because th e PK activity of reticulocytes is much higher than that of mature RBCs , the PK activity in mature RBCs of the mutant CBA mice was calculated to be 2.8% that of mature RBCs of CBA-+/+ mice. Because RBC type PK i s encoded by the Pk-l locus of the mouse (chromosome 3), we designated the mutant locus as Pk-1(slc). The anemia and PK deficiency of CBA-Pk -1(slc)/Pk-1(slc) mice were cured by bone marrow transplantation (BMT) from CBA-+/+ mice. Prior irradiation was not necessary for the curati ve BMT. On the other hand, the BMT from CBA-Pk-1(slc)/Pk-1(slc) mice t o nonirradiated CBA-+/+ mice did not result in the decrease of RBCs an d the reduction of PK activity. The present results indicate that CBA- Pk-1(slc)/Pk-1(slc) mice are a potentially useful animal model for stu dying pathophysiology of PK deficiency and for developing new therapeu tic methods to correct PK deficiency. (C) 1995 by The American Society of Hematology.