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

Conway, AJ; Brown, FC; Hortle, EJ; Burgio, G; Foote, SJ; Morton, CJ; Jane, SM; Curtis, DJ

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

Conway, AJ Brown, FC Hortle, EJ Burgio, G Foote, SJ Morton, CJ Jane, SM Curtis, DJ

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Publisher:: COMPANY OF BIOLOGISTS LTD
Publication Type:: Journal Article
Citation:: Dis Model Mech, 2018, 11, (5), pp. dmm034678
Issue Date:: 2018-05-21

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Field	Value	Language
dc.contributor.author	Conway, AJ
dc.contributor.author	Brown, FC
dc.contributor.author	Hortle, EJ
dc.contributor.author	Burgio, G
dc.contributor.author	Foote, SJ
dc.contributor.author	Morton, CJ
dc.contributor.author	Jane, SM
dc.contributor.author	Curtis, DJ
dc.date.accessioned	2022-09-08T01:29:39Z
dc.date.available	2018-04-18
dc.date.available	2022-09-08T01:29:39Z
dc.date.issued	2018-05-21
dc.identifier.citation	Dis Model Mech, 2018, 11, (5), pp. dmm034678
dc.identifier.issn	1754-8403
dc.identifier.issn	1754-8411
dc.identifier.uri	http://hdl.handle.net/10453/161507
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	COMPANY OF BIOLOGISTS LTD
dc.relation.ispartof	Dis Model Mech
dc.relation.isbasedon	10.1242/dmm.034678
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences
dc.subject.classification	Developmental Biology
dc.subject.mesh	Anemia, Hemolytic
dc.subject.mesh	Anemia, Hemolytic, Congenital Nonspherocytic
dc.subject.mesh	Animals
dc.subject.mesh	Bone Marrow Transplantation
dc.subject.mesh	Carbohydrate Metabolism, Inborn Errors
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Erythrocytes
dc.subject.mesh	Ethylnitrosourea
dc.subject.mesh	Glycolysis
dc.subject.mesh	Homozygote
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Mutant Strains
dc.subject.mesh	Mutagenesis
dc.subject.mesh	Mutation, Missense
dc.subject.mesh	Phenotype
dc.subject.mesh	Triose-Phosphate Isomerase
dc.subject.mesh	Erythrocytes
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Mutant Strains
dc.subject.mesh	Anemia, Hemolytic
dc.subject.mesh	Anemia, Hemolytic, Congenital Nonspherocytic
dc.subject.mesh	Carbohydrate Metabolism, Inborn Errors
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Ethylnitrosourea
dc.subject.mesh	Triose-Phosphate Isomerase
dc.subject.mesh	Bone Marrow Transplantation
dc.subject.mesh	Mutagenesis
dc.subject.mesh	Glycolysis
dc.subject.mesh	Homozygote
dc.subject.mesh	Phenotype
dc.subject.mesh	Mutation, Missense
dc.title	Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	England
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-09-08T01:29:30Z
pubs.issue	5
pubs.publication-status	Published online
pubs.volume	11
utslib.citation.issue	5

Abstract:

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.

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http://hdl.handle.net/10453/161507