RMgmDB - Rodent Malaria genetically modified Parasites

29 September 2011: A new version of genome of the P. falciparum 3D7 strain is now available on GeneDB, and in this new version all genes have been assigned new gene identifiers (gene ID’s; starting with PF3D7_xxxxxxx)
For users of RMgmDB this means:
•    RMgmDB can now be searched using the new PF3D7_ID’s, however only the previous P. falciparum gene identifiers will be displayed.
•    We do not intend to change from the ‘old’ P. falciparum ID’s to the new systematic ID’s as displayed in GeneDB until PlasmoDB have also adopted the new ID’s
•    Links in GeneDB and PlasmoDB (i.e. phenotype information) to both existing and new mutants in RMgmDB are NOT affected
Currently, RMgmDB contains information on nearly 600 different parasite mutants
6 June 2011- Recently a number of new malaria mutant parasites have been published in RMgmDB that show phenotypes with potential relevance for drug/vaccine development.

P. berghei mutants expressing mutated circumsporozoite proteins
- P. berghei mutants expressing circumsporozoite proteins in which the natural H-2K^d restricted epitope is replaced with an H-2K^b restricted epitope. Phenotype analyses of these mutants indicate that the main targets of protective CD8+ T cells are parasite proteins exported to the hepatocyte cytosol. (RMgm-613)
- P. berghei mutants expressing circumsporozoite proteins with mutated ‘region I’. Phenotype analyses of these mutants establish the link between CSP cleavage and hepatocyte invasion and demonstrates that efficient cleavage requires region I (RMgm-608).

P. berghei mutants expressing P. falciparum proteins
- P. berghei mutants expressing the Chloroquine Resistance Transporter (CRT) of the human parasite P. falciparum (RMgm-610, RMgm-611)
- P. berghei mutants expressing the Hexose Transporter 1 (HT1) protein of the human parasite P. falciparum. These mutants have been used to test the sensitivity PfHT1 in vivo to an inhibitor of HT1, the glucose analog C3361 (RMgm-604)

P. berghei mutants lacking expression of potential drug target proteins
P. berghei mutants that lack expression of ‘antioxidant enzymes’ (thioredoxin reducatase and glutathione reductase) demonstrating that these enzymes are not essential for blood stage development.(RMgm-586, RMgm-587, RMgm-403)
P. berghei mutants with disrupted genes that show a developmental defect in sporozoite development and transition into liver stages
- P. berghei mutants lacking genes encoding RNA binding proteins (Pumilio; Puf). Phenotype analyses indicate that the Puf2 protein is a key regulator of the transformation of sporozoites into liver stages (RMgm-514, RMgm-516, RMgm-616, RMgm-617).
- P. berghei mutants lacking genes encoding members of the Cysteine Repeat Modular Protein family (CRMPs). Phenotype analyses show a role in sporozoite egress from oocysts and during liver stage development (RMgm-584, RMgm-585)
- 24 March 2011 - The database contains at this moment information on 540 different mutants
- 23 March 2011 - The RMgm database now also contains ~70 new entries created by piggyBac-mediated mutations/insertions into P. berghei genes (see Fonager, J et al., BMC Genomics (2011) 12:155). Using the search term ‘piggyBac’ in RMgmBD results in a list of ~70 genes which contain piggyBac inserts. The piggyBac inserts were identified using a TAIL PCR approach in DNA collected from blood stage parasites. For all mutated genes the site of integration is indicated as ~20 nucleotides of gene sequence on either site of the TTAA insertion site. Only piggyBac insertions have been included that were found in the open reading frame, 5’UTR (0-500bp from the start codon) or within introns of genes. These piggyBac insertions are expected to affect/disrupt expression of the gene. The presence of an insert may therefore provide indirect evidence that the gene is NOT essential for blood stage development. For this reason we have included this information in RMgmDB. However, neither expression of the target gene nor the phenotype of the mutant parasite containing the insert has been analyzed.
- 28 February 2011 - The database contains at this moment information on more than 460 different mutants. New mutants include mutants with a mutated Cloroquine Resistant Transporter and mutants with a mutated Circumsporozoite Protein.
- 22 October 2010 - The database contains at this moment information on more than 440 different mutants
- 22 October 2010 - Unsuccessful attempts to knock-out P. berghei genes based on the old gene models
  IMPORTANT NOTE:
  The RMgmDB contains information on a large number of (un)published and unsuccessful attempts to knock-out Plasmodium genes. These unsuccessful attempts strongly indicate that these genes may have an essential role during blood stag development. The new P. berghei annotation, in GeneDB, has revealed that for several unsuccessful attempts to knock-out genes the primers for the 5’ and 3’ targeting regions are located in NOT ONE BUT IN TWO neighboring/adjacent genes. Therefore the integration of the DNA-construct would target TWO genes. The failure to disrupt/knock-out the target gene might, therefore, be due to the unintentional disruption of an additional gene. In RMgmDB we have indicated this new information on the unsuccessful attempts where it is now apparent that the targeting construct will disrupt two adjacent genes.
- 22 October 2010 - RMgmDB database now also contains 64 new entries/mutants generated for the analysis of Plasmodium protein kinases, details of this study have recently been published in Cell Host & Microbe (2010, 8:377-87).
- 19 July 2010 - A paper has been published in Trends in Parasitology which describes the (use of the) RMgm-database. Special emphasis is on standardization of mutant generation and describing mutant phenotypes.
- 26 March 2010 - In GeneDB there are direct links from appropriate gene pages to genetically modified rodent malaria parasites in the RMgm database.
- 5 March 2010 - We have now changed from using the previous P. berghei gene models (i.e. PBXXXXX.XX.X) to the new systematic id’s as provided by GeneDB; i.e. PBANKA_xxxxxx). This means:
  - For all mutants only the new gene models will be visible
  - The database can still be searched using old gene models, however only new gene models will be displayed
  - The P. berghei gene models are now linked to GeneDB gene pages (and not to PlasmoDB, as it still uses the old gene models).
  - Existing links in PlasmoDB out to the RMgm database are not affected. Information on new mutant entries will be linked to PlasmoDB once they have adopted the new gene models.
- 29 December 2009 - The database contains at this moment information on more than 300 different mutants.
- 23 July 2009 - In PlasmoDB there are direct links from appropriate gene pages to genetically modified rodent malaria parasites in the RMgm database.
- 16 June 2009 - The database contains at this moment information on more than 260 different mutants.
- 1 April 2009 - The database contains at this moment information on more than 200 different mutants.
- 28 January 2009 - The database contains information on approximately 150 different mutants.
- 6 November 2008 - This database is in its preliminary stages; we are still technically improving the database. At this moment we have information on less then 100 parasite mutant lines.
- 5 October 2008 - The new database, RMgmDB, online!

RMgmDB - Rodent Malaria genetically modified Parasites

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