Genetics of @entity8775 resistance in the rodent XXXX parasite @entity21552 .

@entity5427 @entity21552 @entity8775 @entity3964 @entity311
The genetic determinants of resistance to @entity8775 in @entity311 parasites are unclear. Some studies have implied that amplification of, or mutations in, the multidrug resistance gene pfmdr1 in @entity3964 may be involved. Using the rodent @entity311 model @entity21552 , we investigated the role of the orthologue of this gene, pcmdr1, in a stable @entity8775 -resistant mutant, @entity5427 (15MF/3), selected from a sensitive clone. pcmdr1 exists as a single copy gene on chromosome 12 of the sensitive clone. In @entity5427 (15MF/3), the gene was found to have undergone duplication, with one copy translocating to chromosome 4. mRNA levels of pcmdr1 were higher in the mutant than in the parent sensitive clone. A partial genetic map of the translocation showed that other genes in addition to pcmdr1 had been cotranslocated. The sequences of both copies of pcmdr1 of @entity5427 (15MF/3) were identical to that of the parent sensitive clone. A cross was made between @entity5427 (15MF/3) and an unrelated @entity8775 -sensitive clone, AJ. Phenotypic and molecular analysis of progeny clones showed that duplication and overexpression of the pcmdr1 gene was an important determinant of resistance. However, not all @entity8775 -resistant progeny contained the duplicated gene, showing that at least one other gene was involved in resistance.
