Trypanosoma brucei brucei: characterization of an ODC null bloodstream form mutant and the action of alpha-difluoromethylornithine.
Ornithine decarboxylase (ODC) is a key enzyme in the polyamine synthesis pathway in African trypanosomes. We report here the characterization of an ODC null bloodstream form Trypanosoma brucei brucei mutant, created by replacing the ODC gene with antibiotic resistant marker genes through transfection and homologous recombination. The null mutant expresses no ODC mRNA or protein and does not have ODC enzymatic activity. We tested the attenuation of the bloodstream form ODC- mutants in mice, and showed that these mutants cannot multiply and are quickly cleared from the blood. We also tested the effect of DFMO on this ODC null mutant.
Li
F
F
Department of Medicine, Columbia College of Physicians and Surgeons, New York, New York 10032, USA.
Hua
S B
SB
Wang
C C
CC
Gottesdiener
K M
KM
D000818:Animals; D003470:Culture Media; D004351:Drug Resistance / Q000235:genetics; D000518:Eflornithine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011700:Putrescine / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development
D003470:Culture Media; D014344:Trypanocidal Agents; D009955:Ornithine Decarboxylase; D011700:Putrescine; D000518:Eflornithine