Format

Send to

Choose Destination
Dis Model Mech. 2018 May 21;11(5). pii: dmm034678. doi: 10.1242/dmm.034678.

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

Author information

1
Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne 3004, Australia.
2
The John Curtin School of Medical Research, Australian National University, Canberra 0200, Australia.
3
Australian Cancer Research Foundation Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy 3065, Australia.
4
The Alfred Hospital, Melbourne 3004, Australia.
5
Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne 3004, Australia david.curtis@monash.edu.
6
Central Clinical School, Monash University, Melbourne 3004, Australia.

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.

KEYWORDS:

Anaemia; Erythropoiesis; N-ethyl-N-nitrosourea; TPI deficiency; Transplantation

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center