Mutant/mutation
The mutant lacks expression of purine nucleoside phosphorylase (PNP).
(gene model in P. yoelii YM: PYYM_1115100)

Protein (function)
Unlike their mammalian hosts, malaria parasites cannot synthesize purines de novo and depend exclusively on purine salvage and recycling for RNA and DNA synthesis. The purine salvage pathway is streamlined in Plasmodium, composed of only adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and hypoxanthine-guanine-xanthine phosphoribosyltransferase. Hypoxanthine is a  precursor for all purines and a central metabolite for nucleic acid synthesis in P.  falciparum. The dual action of P. falciparum ADA and PNP for purines and methylthiopurines allows the parasite to form hypoxanthine from host purine pools and to recycle hypoxanthine from methylthioadenosine, a product of polyamine synthesis. P. falciparum ADA and PNP function at the intersection of the polyamine metabolism and purine salvage pathways

Phenotype
All wild type (WT)-infected  mice developed high parasitemias and died within 10 d of challenge. ΔPyPNP and ΔPyPNP-GFP parasites had no detectable impairment of intraerythrocytic development, but growth of these lines was impaired compared to that of WT parasites. None of the parasite lines lacking PNP were lethal to mice, and infected mice recovered from infection with no detectable parasitemia.

No detailed information is provided on gametocyte or ookinete production. Mosquitoes fed on mice with gametocytes showed strongly reduced numbers of oocysts. No sporozoites were found in the salivary gland sporozoites.

Additional information
Two PyPNP-knockout mutants were generated by targeting the WT pnp genomic locus with PCR generated deletion constructs designed to replace the coding region of the pnp gene with either the hdhfr selection cassette (ΔPypnp) or the hdhfr/gfp selection cassette (ΔPypnpGFP) via double cross-over homologous recombination between 5’-fragment and 3’-fragment of the pnp locus that flank the selection cassette.

See also RMgm-837  for a P. berghei ANKA mutant lacking expression of PNP. This mutant  shows normal growth and multiplication of blood stages and parasites induce experimental cerebral malaria in C57BL/6 mice.

Other mutants
RMgm-837: a P. berghei ANKA mutant lacking expression of PNP