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Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice

(2011) PLOS ONE. 6(11).
Author
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Abstract
The use of genetically modified mice, i.e. transgenic as well as gene knockout (KO) and knock-in mice, has become an established tool to study gene function in many animal models for human diseases. However, a gene functions in a particular genomic context. This implies the importance of a well-defined homogenous genetic background for the analysis and interpretation of phenotypes associated with genetic mutations. By studying a Plasmodium chabaudi chabaudi AS (PcAS) malaria infection in mice bearing a TLR9 null mutation, we found an increased susceptibility to infection, i.e. higher parasitemia levels and increased mortality. However, this was not triggered by the deficient TLR9 gene itself. Instead, this disease phenotype was dependent on the heterogeneous genetic background of the mice, which appeared insufficiently defined as determined by single nucleotide polymorphism (SNP) analysis. Hence, it is of critical importance to study gene KO phenotypes on a homogenous genetic background identical to that of their wild type (WT) control counterparts. In particular, to avoid problems related to an insufficiently defined genetic background, we advocate that for each study involving genetically modified mice, at least a detailed description of the origin and genetic background of both the WT control and the altered strain of mice is essential.
Keywords
PLASMODIUM-CHABAUDI-CHABAUDI, EXPERIMENTAL CEREBRAL MALARIA, ACTIVATES DENDRITIC CELLS, AFFECTED SIBLING PAIRS, TOLL-LIKE RECEPTORS, IMMUNE-RESPONSES, B-CELLS, CHROMOSOME 5Q31-Q33, SUSCEPTIBILITY LOCI, INBRED STRAINS

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Chicago
Geurts, Nathalie, Erik Martens, Sebastien Verhenne, Natacha Lays, Greet Thijs, Stefan Magez, Benedicte Cauwe, et al. 2011. “Insufficiently Defined Genetic Background Confounds Phenotypes in Transgenic Studies as Exemplified by Malaria Infection in Tlr9 Knockout Mice.” Plos One 6 (11).
APA
Geurts, N., Martens, E., Verhenne, S., Lays, N., Thijs, G., Magez, S., Cauwe, B., et al. (2011). Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice. PLOS ONE, 6(11).
Vancouver
1.
Geurts N, Martens E, Verhenne S, Lays N, Thijs G, Magez S, et al. Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice. PLOS ONE. 2011;6(11).
MLA
Geurts, Nathalie et al. “Insufficiently Defined Genetic Background Confounds Phenotypes in Transgenic Studies as Exemplified by Malaria Infection in Tlr9 Knockout Mice.” PLOS ONE 6.11 (2011): n. pag. Print.
@article{8131785,
  abstract     = {The use of genetically modified mice, i.e. transgenic as well as gene knockout (KO) and knock-in mice, has become an established tool to study gene function in many animal models for human diseases. However, a gene functions in a particular genomic context. This implies the importance of a well-defined homogenous genetic background for the analysis and interpretation of phenotypes associated with genetic mutations. By studying a Plasmodium chabaudi chabaudi AS (PcAS) malaria infection in mice bearing a TLR9 null mutation, we found an increased susceptibility to infection, i.e. higher parasitemia levels and increased mortality. However, this was not triggered by the deficient TLR9 gene itself. Instead, this disease phenotype was dependent on the heterogeneous genetic background of the mice, which appeared insufficiently defined as determined by single nucleotide polymorphism (SNP) analysis. Hence, it is of critical importance to study gene KO phenotypes on a homogenous genetic background identical to that of their wild type (WT) control counterparts. In particular, to avoid problems related to an insufficiently defined genetic background, we advocate that for each study involving genetically modified mice, at least a detailed description of the origin and genetic background of both the WT control and the altered strain of mice is essential.},
  articleno    = {e27131},
  author       = {Geurts, Nathalie and Martens, Erik and Verhenne, Sebastien and Lays, Natacha and Thijs, Greet and Magez, Stefan and Cauwe, Benedicte and Li, Sandra and Heremans, Hubertine and Opdenakker, Ghislain and Van den Steen, Philippe E},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  language     = {eng},
  number       = {11},
  pages        = {10},
  title        = {Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice},
  url          = {http://dx.doi.org/10.1371/journal.pone.0027131},
  volume       = {6},
  year         = {2011},
}

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