Mutant/mutation
The mutant expresses a mutated form of the circumsporozoite protein (CS).
The mutant expresses CS in which region II-plus of the protein has been substituted with alanines (R290A, K291A, R292A, K293A). Region II-plus is located at the 5' end of the thrombospondin type I repeat (TSR) domain.

Protein (function)
The CS protein is the major protein on the surface of sporozoites and is critical for development of sporozoites within the oocysts and is involved in motility and invasion of both the salivary gland of the mosquito and the liver cells. The protein is also found on the oocyst plasma membrane and on the inner surface of the oocyst capsule. Specific motifs in CS are involved in sporozoite binding to mosquito salivary glands and in sporozoite attachment to heparan sulfate proteoglycans in the liver of the mammalian host. During substrate-dependent locomotion of sporozoites, CS is secreted at the sporozoite anterior pole, translocated along the sporozoite axis and released on the substrate at the sporozoite posterior pole. Following sporozoite invasion of hepatocytes, the CS is released in the host cell cytoplasm.

Phenotype
The phenotype analysis shows that CS is involved in the exit of the sporozoites from the oocysts and that mutation in region II-plus of CS prevents the exit of sporozoites from oocysts. The trypsin-resistant phenotype of the mutant oocysts indicate that sporozoite egress from oocysts is a protease-dependent process. CS is present on the inner surface of the oocyst capsule and it is possible that proteolysis (involving cysteine and/or serine proteases) of the CS protein layer underneath the capsule is required for sporozoite egress. See also mutant RMgm-102 which lacks expression of a papain-like cysteine protease (Egress Cysteine Protease 1; ECP1) which is required for sporozoite egress from sporozoites.
The reduced binding of mutant sporozoites to HepG2 cells in vitro and the lack of infectivity to rats indicate that the Region II-plus is involved in hepatocyte invasion (possibly through binding to heparan sulfate proteoglycans (HSPGs).
A. P. berghei mutant has been described expressing a mutated from of CS of P. falciparum lacking Region II (RMgm-71). Sporozoites of this mutant show no gliding motility, do not invade salivary glands and are not infective to the mammalian host.. A difference between the mutated CS genes is that the Region II-plus deletion in the mutant described here does not affect the thrombospondin (TSR) domain whereas in the RMgm-71 mutant two of the four cysteines of the TSR domain are deleted.

Other mutants
A P. berghei mutant has been generated that lacks expression of CS (RMgm-9) .
A P. berghei mutant has been generated that produces reduced levels of CS (RMgm-72).
P. berghei mutants have been generated with a mutated GPI-anchor addition sequence (RMgm-73).
A P. berghei mutant has been generated in which the endogenous P. berghei CS was replaced with P. falciparum CS (RMgm-69).
Two P. berghei mutants have been generated that express mutated forms of P. falciparum CS (RMgm-70 with a mutated Region I; RMgm-71 with a mutated Region II).
A P. berghei mutant has been generated that express a hybrid form of CS of P. berghei and  P. falciparum (the P. berghei CS repeat region  is exchanged with the P. falciparum CS repeat region)(RMgm-76).
A P. berghei mutant has been generated in which the endogenous P. berghei CS was replaced with P. gallinaceum CS (RMgm-74).
A P. berghei mutant has been generated in which the endogenous P. berghei CS was replaced with P. yoelii CS (RMgm-75).