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

This is the authors' abstract. We don't add key points for this paper.

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.