Mutant/mutation
The mutant lacks expression of HRF and expresses GFP (no details are provided on the regulatory elements controlling GFP expression).

Protein (function)
Histamine releasing factor (HRF), originally classified as a tumor protein (translationally controlled tumor protein, TCTP) in mouse erythroleukemia, is found in a wide range of eukaryotes including yeast, plants and animals. The name TCTP was coined as a consequence of cDNA cloning from a human mammary carcinoma and based on the fact that TCTP is regulated at the translational level. HRF plays many different functions and is involved in many physiological processes such as cell proliferation, stress and heat shock responses, and cell death. As an intracellular product, HRF has a calcium and tubulin binding properties and has been shown to transiently associate with microtubules during cell cycle. As a calcium-binding protein HRF was found to be up-regulated in response to a loss of calcium homeostasis which could be part of a role of HRF in general stress response.
As a secreted product, HRF has immuno-modulatory roles. In humans, HRF induces the release of histamine and modulates cytokine secretion from basophils, eosinophils, and T cells. HRF stimulates eosinophils to produce IL-8, induces secretion of IL-4 and IL-13 from basophils and inhibits IL-2, IL-4, and IL-13 production from stimulated primary T cells (Vonakis et al., 2003). Recently, HRF was found to have an inflammatory role in mouse models of asthma and allergy and to exist as a dimer bound to a subset of IgE and IgG antibodies, suggesting the possibility for HRF to cross-link IgE on the surface of basophils and mast cells.
HRF is also expressed by a number of eukaryotic parasites, including Plasmodium.
Plasmodium HRF, which has a high homology to human HRF (their amino acid sequences are 33% identical and 54% similar) has been proposed to play an important role during the erythrocytic phase of malarial infection (MacDonald et al., 2001).

Phenotype
(Most) C57BL/6 mice infected with PbNK65-hrfΔ resolve blood stage infections. Parasites are cleared from infection around day 13/14 after infection. Clearance is dependent on the infection dose (mice infected with a low dose of 10(3)parasites did not lead to parasite clearance). In contrast, all mice infected with wild type NK65 die from severe complications (around day 20 after infection).

Additional information
PbNK65-hrfΔ mice that cleared infections were protected against re-infection. Evidence is presented that lack of HRF expression causes an IL-6 increase, which boosts T and B cell responses to resolve infection and leave a cross-stage, cross-species, and lasting immunity. Evidence is presented that mutant-induced protection involves a combination of antiparasite IgG2c antibodies and FcγR+ CD11b+ cell phagocytes, especially neutrophils, which are sufficient to confer protection.

Other mutants
RMgm-1135: a P. berghei ANKA mutant lacking expression of HRF