Mutant/mutation
The mutant lacks expression of SLARP (sporozoite and liver stage asparagine-rich protein; SAP1, sporozoite asparagine-rich protein; S22).

Protein (function)
SLARP was first identified as a sporozoite-expressed gene in a suppression subtractive hybridization (SSH) screen of P.  yoelii salivary gland sporozoites versus blood-stage merozoites (designated S22, sporozoite-specific gene 22).

Phenotype
The phenotype analyses indicate an essential role during the transformation of the sporozoite into the liver trophozoite within the hepatocyte. The lack of expression of SLARP/SAP1  results in complete loss of sporozoite infectivity to rodents, due to early developmental arrest after invasion of hepatocytes. Mutant sporozoites productively invade host cells by forming a parasitophorous vacuole (PV), but subsequent remodelling of the membrane of the PV (PVM) is impaired as a consequence of down-regulation of genes encoding PVM-resident proteins.
Mutant salivary gland sporozoites showed strongly reduced transcript abundance for several genes encoding proteins that play a role in infection of the liver (UIS3, UIS4). Based on these observations and its association with the nucleus it has been suggested that SAP1 plays a role in translational repression of transcripts in sporozoites. See also 'Additional Information'  for a possible different function of SLARP/SAP1.

Additional information
Staining with the cholesterol-binding agent filipin confirmed the presence of a parasitophorous vacuole membrane (PVM) in infected hepatocytes invaded by the mutant sporozoites. By IFA analysis only very weak internal staining was observed with antibodies against UIS4 and no staining with EXP1 antibodies, indicating that remodelling of the PVM is impaired.

Immunization of mice with the attenuated sporozoites of the mutant parasites induced only limited protective immune responses against challenge with wild type parasites. See also RMgm-185, a P. yoelii mutant lacking expression of SAP1/SLARP. Immunization with P. yoelii mutant sporozoites induces strong protective immunity.

Using a mutant that expresses an mCherry tagged version of SAP1/SLARP (RMgm-186) a nuclear location/association of SLARP/SAP1 was observed. Based on these observations it has been suggested that SAP1/SLARP functions as a specific regulator of the expression of genes involved at early steps of liver stage development.
See also the phenotype description of mutant RMgm-172 lacking expression of SAP1/SLARP By IFA analysis using antibodies against SAP1 a specific sporozoite-internal staining was observed that excluded the nucleus and was distinct from circumsporozoite (CS) protein staining, suggesting a cytoplasmic location. Based on these observations and its cytoplasmic location it has been suggested that SAP1 plays a role in translational repression of transcripts in sporozoites.

Genbank accession no. EU579524.

Other mutants
RMgm-172: An independent mutant lacking expression of SAP1/SLARP
RMgm-186: mutant expressing mCherry tagged SAP1/SLARP