Bone marrow transplantation corrects haemolytic anaemia in novel ENU mutagenesis mouse model of TPI deficiency

Abstract

We have performed a genome-wide ENU mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes for the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice that closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wildtype donor cells, which restored all haematological parameters and increased red cell enzyme function to wildtype levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency demonstrating that the haematological phenotype can be rescued.