| 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) : 20852334
|
| 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 cl15cy1
|
| Other information parent line | A reference wild type clone from the ANKA strain of P. berghei (PubMed: PMID: 17406255). |
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| The mutant parasite was generated by |
| Name PI/Researcher | K. Buchholz; K. Becker; K. Matuschewski |
| Name Group/Department | Interdisciplinary Research Centre |
| Name Institute | Justus-Liebig University |
| City | Giessen |
| Country | Germany |
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| Name of the mutant parasite |
| RMgm number | RMgm-586 |
| Principal name | TrxR(-) |
| 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. Total number of midgut sporozoites was lower compared to midgut-sporozoite production of wild type parasites. The number of salivary gland sporozoites was comparable to wild type. |
| Sporozoite | Normal numbers of oocysts. Total number of midgut sporozoites was lower compared to midgut-sporozoite production of wild type parasites. The number of salivary gland sporozoites was comparable to wild type. In vivo and in vitro infectivity (as measured by prepatent period in mice and in vitro development in HuH7 hepatoma cells) of isolated sporozoites was comparable to that of wild type sporozoites. Infectivity of mosquitoes infected with mutant parasites was lower than that of mosquitoes infected with wild type parasites |
| Liver stage | In vivo and in vitro infectivity (as measured by prepatent period in mice and in vitro development in HuH7 hepatoma cells) of isolated sporozoites was comparable to that of wild type sporozoites. Infectivity of mosquitoes infected with mutant parasites was lower than that of mosquitoes infected with wild type parasites |
| Additional remarks phenotype | Mutant/mutation
The mutant lacks expression of thioredoxin reductase (TrxR)
Protein (function)
Plasmodium parasites have a dual antioxidative system based on the cysteine- containing redox-active peptides glutathione (GSH) and thioredoxin (Trx). Glutathione is the major low molecular weight antioxidant in Plasmodium parasites, and it is kept at a high level in the reduced state by the antioxidant enzyme glutathione reductase (GR). Phenotype analyses of mutants lacking either expression of GR (RMgm-403, RMgm-404, RMgm-587) or of gamma-glutamylcysteine synthase (RMgm-γ-GCS; 204) has provided evidence that GSH metabolism is critical for development of the mosquito oocyst stage. Expression of GR or γ-GCS was not essential for the survival of the blood stages. In addition to the GSH system, a complete Trx system, consisting of NADPH, thioredoxin reductase (TrxR), Trx, and a number of Trx-dependent peroxidases, has been characterized in Plasmodium.
Phenotype
The phenotype analyses indicate a non-essential role of TrxR during blood stage development, mosquito development and development in the liver under normal growth conditions.
Additional information
It has been reported that it was impossible to disrupt the trxr gene of P. falciparum indicating that TrxR is essential for P. falciparum blood stages during in vitro development (Krnajski et al., 2002, J. Biol. Chem 277, 25970-975) . Possible explanations for the different results in the P. falciparum studies and the results presented here include (i) frequently observed technical problems in the P. falciparum transfection system, (ii) an important role of TrxR for Plasmodium under in vitro culture conditions (which only partially reflect the physiological environment and lack feed-back regulation by the host), or (iii) a different role of TrxR in rodent and primate/human parasites
Other mutants |
*RMgm-586
