Triosephosphate isomerase activity-deficient mice show haemolytic anaemia in homozygous condition.
A triosephosphate isomerase (TPI) mutant, Tpi1(a-m6Neu), with approximately 57% residual enzyme activity in blood compared with wild-type was detected among offspring of triethylenemelamine-treated male mice. Homozygous mutants with about 13% residual enzyme activity were recovered in progeny of inter se matings of heterozygotes. The loss of TPI activity was evident both in blood and in other tissue extracts. Values for haematocrit, haemoglobin, number of red blood cells (RBC), mean corpuscular volume of RBC, mean corpuscular haemoglobin concentration and spleen weight show significant differences between wild-type animals and homozygous mutants. Sequence analysis revealed a substitution (c.A149G) in the Tpi1 gene. This mutation results in an Asp to Gly substitution at codon 49 in exon 2 at a highly conserved position located in the functional domain of the TPI protein which is responsible for the correct dimerization of the subunits. As a potential animal model, Tpi1(a-m6Neu) represents the only available TPI-deficient homozygous viable mouse mutation.
Pretsch
Walter
W
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany. pretsch@helmholtz-muenchen.de
D000743:Anemia, Hemolytic / Q000235:genetics*; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006720:Homozygote; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D014305:Triose-Phosphate Isomerase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D014305:Triose-Phosphate Isomerase