Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.
Dis Model Mech
; 11(5)2018 05 21.
Article
em En
| MEDLINE
| ID: mdl-29720471
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 7â
weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triose-Fosfato Isomerase
/
Erros Inatos do Metabolismo dos Carboidratos
/
Mutagênese
/
Transplante de Medula Óssea
/
Anemia Hemolítica
/
Anemia Hemolítica Congênita não Esferocítica
Limite:
Animals
Idioma:
En
Revista:
Dis Model Mech
Ano de publicação:
2018
Tipo de documento:
Article