Mutant/mutation
The mutant lacks expression of MRP2 and expresses GFP under control of a male gametocyte specific promoter and RFP under the control of a female gametocyte specific promoter. 

Protein (function)
The genome of the human malaria parasite Plasmodium falciparum encodes sixteen ABC family members.

ATP binding cassette (ABC) transport proteins are evolutionary well conserved membrane transporters that translocate structurally and functionally diverse compounds at the expense of ATP, even against steep concentration gradients. The structure of a typical ABC transporter is composed of two transmembrane domains (TMDs), each consisting of six transmembrane helices (TM) and two cytosolic nucleotide binding domains (NBDs). Most of the ABC family members act as efflux systems and are therefore predominantly located on plasma membranes. These transport proteins are well known for their role in multidrug resistance, as many classes of drugs are among their substrates. Mutations or upregulation of genes encoding ABC transporters may enhance efflux and decrease intracellular drug accumulation, ultimately resulting in resistance. ABC proteins are classified into seven subfamilies (A-G), which can be distinguished upon phylogenetic analysis of the conserved NBDs and have differential compound specificities.

Proteins of the ABC transporter subfamily C (ABCC) are often referred to as the MRPs (multidrug resistance-associated proteins). The human MRP family consists of 13 members. These transporters predominantly translocate organic anions across the plasma membrane, including glutathione-, glucuronate- or sulfate- conjugates from endogenous and exogenous sources as well as cyclic nucleotides, leukotriens and prostaglandins that are involved in cellular signaling processes. Several MRP proteins are known to transport drugs and are involved in resistance acquisition.

The sequenced Plasmodium genomes contain either one or two genes encoding C-family ABC transport proteins. Human and non-human primate malaria parasites possess two genes, whereas rodent parasites have one gene. In P. falciparum, PF3D7_0112200 and PF3D7_1229100, encode the multidrug resistance protein 1 (PfMRP1) and 2 (PfMRP2), respectively. These proteins have 41% sequence identity at the amino acid level. Characterization by phylogenetic analysis of the highly conserved nucleotide binding domain (NBD), which consists of the Walker A, ABC signature and Walker B regions, showed 47.2% and 57.0% identity of the first and second NBD regions, respectively. The single P. berghei mrp gene (PBANKA_144380) has a syntenic genome location with Pfmrp2. DNA sequence alignment of PBANKA_144380 with Pfmrp1 and Pfmrp2 shows 36.7% and 42.0% identity, respectively. The higher sequence similarity of PBANKA_144380 in combination with its syntenic location with Pfmrp2 suggests that it is the functional ortholog of Pfmrp2

Phenotype
Normal development of asexual stages. Reduced gametocyte production resulting in lower production of ookinetes, oocysts and sporozoites.

Normal gliding motility of sporozoites and invasion of hepatocytes by mutant sporozoites.

Liver stages completely abort development during mid- to late liver stage development. During the first 24-30 h the development of PbΔmrp2 liver stages with respect to number, size and number of nuclei per parasite was similar to WT liver stage development. In contrast, subsequent intra-hepatocytic development of PbΔmrp2 parasites was abnormal. While parasites appear to invade and develop like WT parasites until 30 hpi, they become  significantly smaller from 40 hpi and contain fewer nuclei than WT parasites at 52 hpi. While expression of the PVM protein EXP1 was readily detected in PbΔmrp2 parasites, the liver stages remained MSP1-negative during the complete culture period. The combined observations demonstrate that ΔPbmrp2 parasites can invade hepatocytes, establish a PVM and start nuclear division but are unable to form mature schizonts containing infectious merozoites.

Additional information
Intravenous injection of 5x10⁴‐3x10⁵ purified PbΔmrp2 salivary gland sporozoites (2 experiments; 14 C57Bl/6 mice) did not result in a blood stage infection.

Other mutants
RMgm-1322: A mutant expressing a C-terminal cmyc-tagged version of MRP2
RMgm-1321: An independent mutant lacking expression of MRP2. This mutant expresses GFP under control of the constitutive eef1a promoter.