Mutant/mutation
The mutant contains 2 additional copies of the macrophage migration inhibitory factor gene (mif) of P. yoelii integrated into the c-ssu-rrna gene locus. These mif copies are under control of the strong constitutive eef1a promoter.

Protein (function)
Macrophage migration inhibitory factor (MIF) is a mammalian cytokine that participates in innate and adaptive immune responses. Homologues of mammalian MIF have been discovered in parasite species (nematodes and malaria parasites). Like human MIF, histidine-tagged purified recombinant PMIF shows tautomerase and oxidoreductase activities (although the activities are reduced compared to those of histidine-tagged human MIF) and efficiently inhibits AP-1 activity in human embryonic kidney cells (Augustijn et al., Infect Immun. (2007),75:1116-28). P. berghei MIF is expressed in both the mammalian host and mosquito vector. In blood stages, MIF is secreted into the infected erythrocytes and released upon schizont rupture.
See also RMgm-26 for a P. berghei mutant lacking expression of MIF. This mutant was able to complete the entire life cycle and exhibited no significant changes in growth characteristics or virulence features during blood stage infection. However, rodent hosts infected with this mutant had significantly higher numbers of circulating reticulocytes.

Phenotype
Analyses of the course of infection of the mutant parasites in two mice strains (see 'Additional information') indicate that increased expression of Plasmodium MIF during blood-stage malaria does not increase the severity of disease but may in fact attenuate parasite virulence.

See also the phenotype of mutant RMgm-583. This mutant contains one additional copy of the macrophage migration inhibitory factor gene (mif) of P. yoelii integrated into the dhfr/ts gene locus.

Additional information
By immunoblot analysis and quantitation by densitometry, the PyMIF protein level in Py17X-MIF(+) transgenic parasites was increased approximately 5.5 fold over wt P. yoelii 17X parasites

BALB/cByJ and C57BL/6 mice challenged with Py17X-MIF(+) parasites showed a modest decrease in the severity of infection. The mean peak parasitemia in BALB/cByJ mice infected with Py17X-MIF(+) parasites was 21.7% ± 11.7 compared to 30.9% ± 6.8 in wt infected control mice. Similarly, the mean peak parasitemia in Py17X-MIF(+)  infected C57BL/6 mice was 15.5% ± 7.4, significantly lower than the mean peak parasitemia of 25.0% ± 11.5% observed in wt infected control mice. In both strains of mice  no difference in the pre-patent period of infection, the slope of the ascending parasitemia curve, day 8 parasitemia or day 10 parasitemia was noted between mice infected with Py17X-MIF(+) and wt infected mice. As such, the in vivo growth rate of the two transgenic parasites during the first 8-10 days of infection was comparable. These data indicate that increased expression of Plasmodium MIF during blood-stage malaria does not increase the severity of disease but may in fact attenuate parasite virulence.

Other mutants
RMgm-583: A P. yoelii (17XL) mutant containing one additional copy of the macrophage migration inhibitory factor gene (mif) of P. yoelii integrated into the dhfr/ts gene locus
RMgm-665: A P. yoelii (17XNL) mutant lacking expression of MIF
RMgm-26: a P. berghei mutant lacking expression of MIF.
RMgm-27: a transgenic P. berghei mutant expressing GFP-tagged MIF.
RMgm-31: a P. berghei transgenic mutant expressing c-myc-tagged MIF.