Mutant/mutation
The mutant lacks expression cyclic nucleotide phosphodiesterase, putative (PDEδ, phosphodiesterase delta; cyclic nucleotide phosphodiesterase, putative).

Protein (function)
The following different genes encoding proteins with homology to cyclic nucleotide phosphodiesterase have been identified in Plasmodium

Phenotype
The phenotype analyses indicate that the PDEδ has a crucial role in ookinete development and motility, resulting in failure of invasion of the midgut epithelium and the formation of oocysts. Analyses indicate indicate the lack of expression of PDEδ does not affect motor activity, but as a result of changed cellular morphology it reduced forward gliding which may explain the marked reduction in mosquito transmission of the ookinetes (see 'Additional information').

Additional information
Mutant ookinetes with normal morphology moved at speeds comparable to wild type, while round mutant ookinetes produced little or no forward motility. Conversely, rotational speed increased with the severity of the morphological defect, such that round mutant ookinetes were seen to rotate rapidly on the spot. These analyses indicate that disruption of pdeδ did not affect motor activity, but as a result of changed cellular morphology it reduced forward gliding which may explain the marked reduction in mosquito transmission of the ookinetes.

Aberrant differentiation of mutant ookinetes was not accompanied by parasite death, as judged by exclusion of the membrane impermeable SYTOX® green nucleic acid stain. In addition, injection of mutant ookinetes in the hemocoel, the ookinetes were able to produce oocysts and produced infective salivary gland sporozoites comparable to wild type ookinetes.

Ultrastructural analyses of mutant ookinetes indicated the presence of a 'discontinuous' inner membrane complex (IMC) with gaps that varied in size

In the paper evidence is presented that in ookinetes GCß is the main source for cGMP and that a cyclic GMP signalling module exists that regulates gliding motility of ookinetes. This evidence is partly based on the analysis of the mutant described here lacking expression PDEδ and a mutant lacking expression of both GCβ and PDEδ (RMgm-309). These analyses indicate that PDEδ is the relevant cGMP degrading enzyme. Signalling via a cGMP-dependent protein kinase (PKG; PF14_0346; PB000726.02.0) may regulate ookinete differentiation and motility.

Other mutants
RMgm-309: A mutant lacking expression of both PDEδ and guanylyl cyclase β (GCβ; (Gene models for GCß PB000752.03.0; PB300849.03.0; PB001059; MAL13P1.301).
RMgm-310: A mutant lacking expression of both PDEδ and CDPK3 (calcium-dependent protein kinase-3; PB000947.00.0;PFC0420w).