Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency
Open Access
- 1 May 2018
- journal article
- research article
- Published by The Company of Biologists in Disease Models & Mechanisms
- Vol. 11 (5), dmm034678
- https://doi.org/10.1242/dmm.034678
Abstract
In this study, we performed a genome-wide N-ethyl-N-mtrosourea (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.Keywords
Funding Information
- National Health and Medical Research Council (382900)
This publication has 32 references indexed in Scilit:
- Hsp70- and Hsp90-mediated proteasomal degradation underlies TPIsugarkill pathogenesis in DrosophilaNeurobiology of Disease, 2010
- Triose phosphate isomerase deficiency associated with two novel mutations in TPI geneEuropean Journal of Haematology, 2010
- Features and development of CootActa Crystallographica Section D-Biological Crystallography, 2010
- Triosephosphate isomerase deficiency: New insights into an enigmatic diseaseBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2009
- Triosephosphate isomerase activity-deficient mice show haemolytic anaemia in homozygous conditionGenetics Research, 2009
- Sequencing and genotypic analysis of the triosephosphate isomerase (TPI1) locus in a large sample of long-lived GermansBMC Genomic Data, 2008
- Triose Phosphate Isomerase Deficiency Is Caused by Altered Dimerization–Not Catalytic Inactivity–of the Mutant EnzymesPLOS ONE, 2006
- Drosophila Model of Human Inherited Triosephosphate Isomerase Deficiency Glycolytic EnzymopathyGenetics, 2006
- Hematologically Important Mutations: Triosephosphate IsomeraseBlood Cells, Molecules, and Diseases, 1996
- Three hTIM Mutants that Provide New Insights on why TIM is a DimerJournal of Molecular Biology, 1996