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

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-defi...

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Autores principales:	Nathalie Geurts, Erik Martens, Sebastien Verhenne, Natacha Lays, Greet Thijs, Stefan Magez, Bénédicte Cauwe, Sandra Li, Hubertine Heremans, Ghislain Opdenakker, Philippe E Van den Steen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17c23f85bcdb468db28ebdc787e462a0
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spelling	oai:doaj.org-article:17c23f85bcdb468db28ebdc787e462a02021-11-18T07:34:30ZInsufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.1932-620310.1371/journal.pone.0027131https://doaj.org/article/17c23f85bcdb468db28ebdc787e462a02011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22096530/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Nathalie GeurtsErik MartensSebastien VerhenneNatacha LaysGreet ThijsStefan MagezBénédicte CauweSandra LiHubertine HeremansGhislain OpdenakkerPhilippe E Van den SteenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27131 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathalie Geurts Erik Martens Sebastien Verhenne Natacha Lays Greet Thijs Stefan Magez Bénédicte Cauwe Sandra Li Hubertine Heremans Ghislain Opdenakker Philippe E Van den Steen Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.
description	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.
format	article
author	Nathalie Geurts Erik Martens Sebastien Verhenne Natacha Lays Greet Thijs Stefan Magez Bénédicte Cauwe Sandra Li Hubertine Heremans Ghislain Opdenakker Philippe E Van den Steen
author_facet	Nathalie Geurts Erik Martens Sebastien Verhenne Natacha Lays Greet Thijs Stefan Magez Bénédicte Cauwe Sandra Li Hubertine Heremans Ghislain Opdenakker Philippe E Van den Steen
author_sort	Nathalie Geurts
title	Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.
title_short	Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.
title_full	Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.
title_fullStr	Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.
title_full_unstemmed	Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.
title_sort	insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in tlr9 knockout mice.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/17c23f85bcdb468db28ebdc787e462a0
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Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice.

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