| First Author | Conway AJ | Year | 2018 |
| Journal | Dis Model Mech | Volume | 11 |
| Issue | 5 | PubMed ID | 29720471 |
| Mgi Jnum | J:263104 | Mgi Id | MGI:6159514 |
| Doi | 10.1242/dmm.034678 | Citation | Conway AJ, et al. (2018) Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency. Dis Model Mech 11(5):dmm034678 |
| abstractText | In this study, we performed a genome-wide N-ethyl-N-nitrosourea (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 the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type 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. |
