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Molecular cloning of the X-chromosome located LPS-resistance gene of SPRET/Ei mice: Tsc22d3/Gilz as a candidate gene

Iris Pinheiro (UGent)
(2011)
Author
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(UGent) and (UGent)
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Abstract
Sepsis is an overwhelming systemic inflammatory response of the host to infection, and despite the recent advances in critical care medicine, it is still a leading cause of death in intensive care units in developed countries. Lipopolysaccharide (LPS) or endotoxin, is the principal component of the outer membrane of Gram-negative bacteria, and is per se capable of reproducing several features of a Gram-negative infection, including fever, shock and other characteristics of severe sepsis, as organ dysfunction and hypotension. SPRET/Ei, an inbred mouse strain derived from Mus spretus, is highly resistant to both LPS and Gram-negative bacterial infections, and is therefore a useful model on the discovery of new targets for sepsis treatment. In the present study we show that SPRET/Ei LPS-resistance is linked to the X chromosome, most precisely to a locus located between 55 and 70 cM. Moreover, we have recently shown that SPRET/Ei LPS-resistance can be completely abolished by blocking the signaling mediated by the glucocorticoid receptor (GR). The most well-known gene responding to the signaling initiated by the binding of glucocorticoids to its receptor, the GR, is Tsc22d3/Gilz. Gilz is an important anti-inflammatory gene, and these effects were shown to be largely mediated by repressing NF-B- and AP-1-dependent gene transcription. Gilz is located on the X chromosome in the region defined by the linkage analysis as the one containing the SPRET/Ei gene(s) responsible for its resistance to LPS. GILZ mRNA and protein induction after LPS seem to be organ-specific. For example, it seems to be upregulated by LPS in the lung and downregulated in the liver. Moreover, in both organs, but particularly in the lung, Gilz mRNA expression is higher in SPRET/Ei mice and (BxS)F1 females, when compared to C57BL/6 mice and (BxS)F1-males. Different tools are currently being developed to confirm the importance of this gene in SPRET/Ei LPS-resistance. Altogether, we believe that these results may be of potential interest for future therapeutic application for the treatment of sepsis.

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Citation

Please use this url to cite or link to this publication:

Chicago
Pinheiro, Iris. 2011. “Molecular Cloning of the X-chromosome Located LPS-resistance Gene of SPRET/Ei Mice: Tsc22d3/Gilz as a Candidate Gene”. Ghent, Belgium: Ghent University. Faculty of Sciences.
APA
Pinheiro, I. (2011). Molecular cloning of the X-chromosome located LPS-resistance gene of SPRET/Ei mice: Tsc22d3/Gilz as a candidate gene. Ghent University. Faculty of Sciences, Ghent, Belgium.
Vancouver
1.
Pinheiro I. Molecular cloning of the X-chromosome located LPS-resistance gene of SPRET/Ei mice: Tsc22d3/Gilz as a candidate gene. [Ghent, Belgium]: Ghent University. Faculty of Sciences; 2011.
MLA
Pinheiro, Iris. “Molecular Cloning of the X-chromosome Located LPS-resistance Gene of SPRET/Ei Mice: Tsc22d3/Gilz as a Candidate Gene.” 2011 : n. pag. Print.
@phdthesis{1891614,
  abstract     = {Sepsis is an overwhelming systemic inflammatory response of the host to infection, and despite the recent advances in critical care medicine, it is still a leading cause of death in intensive care units in developed countries. Lipopolysaccharide (LPS) or endotoxin, is the principal component of the outer membrane of Gram-negative bacteria, and is per se capable of reproducing several features of a Gram-negative infection, including fever, shock and other characteristics of severe sepsis, as organ dysfunction and hypotension. SPRET/Ei, an inbred mouse strain derived from Mus spretus, is highly resistant to both LPS and Gram-negative bacterial infections, and is therefore a useful model on the discovery of new targets for sepsis treatment.
In the present study we show that SPRET/Ei LPS-resistance is linked to the X chromosome, most precisely to a locus located between 55 and 70 cM. Moreover, we have recently shown that SPRET/Ei LPS-resistance can be completely abolished by blocking the signaling mediated by the glucocorticoid receptor (GR). The most well-known gene responding to the signaling initiated by the binding of glucocorticoids to its receptor, the GR, is Tsc22d3/Gilz. Gilz is an important anti-inflammatory gene, and these effects were shown to be largely mediated by repressing NF-\unmatched{f06b}B- and AP-1-dependent gene transcription. Gilz is located on the X chromosome in the region defined by the linkage analysis as the one containing the SPRET/Ei gene(s) responsible for its resistance to LPS. GILZ mRNA and protein induction after LPS seem to be organ-specific. For example, it seems to be upregulated by LPS in the lung and downregulated in the liver. Moreover, in both organs, but particularly in the lung, Gilz mRNA expression is higher in SPRET/Ei mice and (BxS)F1 females, when compared to C57BL/6 mice and (BxS)F1-males. Different tools are currently being developed to confirm the importance of this gene in SPRET/Ei LPS-resistance. Altogether, we believe that these results may be of potential interest for future therapeutic application for the treatment of sepsis.},
  author       = {Pinheiro, Iris},
  language     = {eng},
  pages        = {248, 8},
  publisher    = {Ghent University. Faculty of Sciences},
  school       = {Ghent University},
  title        = {Molecular cloning of the X-chromosome located LPS-resistance gene of SPRET/Ei mice: Tsc22d3/Gilz as a candidate gene},
  year         = {2011},
}