| Successful modification | The parasite was generated by the genetic modification |
| The mutant contains the following genetic modification(s) |
Gene disruption
|
| Reference (PubMed-PMID number) |
Reference 1 (PMID number) : 18761621
|
| MR4 number |
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| Parent parasite used to introduce the genetic modification |
| Rodent Malaria Parasite | P. berghei |
| Parent strain/line | P. berghei ANKA |
| Name parent line/clone |
P. berghei ANKA 2.34
|
| Other information parent line | P. berghei ANKA 2.34 is a cloned, gametocyte producer line of the ANKA strain (PubMed: PMID: 15137943). |
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| The mutant parasite was generated by |
| Name PI/Researcher | A. Ecker; R.E. Sinden |
| Name Group/Department | Division of Cell and Molecular Biology |
| Name Institute | Imperial College |
| City | London |
| Country | United Kingdom |
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| Name of the mutant parasite |
| RMgm number | RMgm-98 |
| Principal name | ∆lap5 |
| Alternative name | |
| Standardized name | |
| Is the mutant parasite cloned after genetic modification | Yes |
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| Phenotype |
| Asexual blood stage | Not different from wild type |
| Gametocyte/Gamete | Not different from wild type |
| Fertilization and ookinete | Not different from wild type |
| Oocyst | 'Normal' numbers of oocysts are produced: 189% of wild type (86-298%). Sporozoite formation (sporulation) is strongly affected in the 'mature' oocysts. Most oocysts appear either immature/enlarged or degenerate/vacuolated. |
| Sporozoite | Very low numbers of sporozoites are produced: 3.3% of wild type (0.9-7.8%). No tramission to C57BL/6 mice by mosquito bite |
| Liver stage | Not tested |
| Additional remarks phenotype | Mutant/mutation
The mutant lacks expression of LAP5 (FNPA)
Protein (function)
The lap5 gene is a member of a small conserved gene family, encoding proteins with multiple adhesive domains, for example a Lgl1 (LCCL)-lectin adhesive domain. In P. falciparum the LCCL domain-containing proteins are termed PfCCp's. LAP5 lacks the LCCL domain but has a domain architecture that indicates a vertical relationship with
PfCCp5/LAP3. It contains a fibronectin type 2 domain and an anthrax protective antigen N-terminal domain (Lavazec, C. et al., 2008, Mol. Biochem. Parasitol. 163, 1-7).
The LAP5 (FNPA) protein is detected in a proteome analysis of ookinetes.
Phenotype
Phenotype analyses indicate a role during oocyst development and sporozoite formation/production (see also additional information).
Additional information
Crossings of the mutant females with wild type males did not rescue the formation/production of sporozoites. Crossing of the mutant males with wild type females resulted in wild type production of sporozoites that were infectious to C57BL/6 mice.
Crossings between other mutants have shown that wild type males can rescue defects in females that affect ookinete invasion and traversal of the midgut wall at 18-30 hours after fertilization. The lack of rescue of the ∆lap5 mutant phenotype by crossing of mutant females with wild type males is suggestive of a role of LAP5 within a few hours after fertilization.
Other members of the LAP/CCp family of proteins have been analyzed by targeted gene disruption. A number of mutants lacking expression of these proteins show a comparable defect in development of oocysts and formation of sporozoites (RMgm-113, RMgm-114, RMgm-115: LAP1/PbSLAP/PbSR/CCp3; RMgm-118: LAP2/CCp1; RMgm-119: LAP4/CCp2; RMgm-120: LAP6, CCp4).
Other mutants |
*RMgm-98
