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LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome

Iris Pinheiro (UGent) , Lien Dejager (UGent) , Ioanna Petta (UGent) , Sofie Vandevyver (UGent) , Leen Puimège (UGent) , Tina Mahieu, Marlies Ballegeer (UGent) , Filip Van Hauwermeiren (UGent) , Carlo Riccardi, Marnik Vuylsteke (UGent) , et al.
(2013) EMBO MOLECULAR MEDICINE. 5(3). p.456-470
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Abstract
Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis.
Keywords
INDUCED LEUCINE-ZIPPER, SPLENIC IMMUNE FUNCTIONS, X chromosome, SPRET/Ei, LPS, inflammation, Gilz, FEMALES, PROTEIN, SEPSIS, EXPRESSION, MOUSE STRAIN SPRET/EI, FACTOR-KAPPA-B, GLUCOCORTICOID-RECEPTOR, ALVEOLAR MACROPHAGES

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Chicago
Pinheiro, Iris, Lien Dejager, Ioanna Petta, Sofie Vandevyver, Leen Puimège, Tina Mahieu, Marlies Ballegeer, et al. 2013. “LPS Resistance of SPRET/Ei Mice Is Mediated by Gilz, Encoded by the Tsc22d3 Gene on the X Chromosome.” Embo Molecular Medicine 5 (3): 456–470.
APA
Pinheiro, I., Dejager, L., Petta, I., Vandevyver, S., Puimège, L., Mahieu, T., Ballegeer, M., et al. (2013). LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome. EMBO MOLECULAR MEDICINE, 5(3), 456–470.
Vancouver
1.
Pinheiro I, Dejager L, Petta I, Vandevyver S, Puimège L, Mahieu T, et al. LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome. EMBO MOLECULAR MEDICINE. 2013;5(3):456–70.
MLA
Pinheiro, Iris, Lien Dejager, Ioanna Petta, et al. “LPS Resistance of SPRET/Ei Mice Is Mediated by Gilz, Encoded by the Tsc22d3 Gene on the X Chromosome.” EMBO MOLECULAR MEDICINE 5.3 (2013): 456–470. Print.
@article{3182293,
  abstract     = {Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis.},
  author       = {Pinheiro, Iris and Dejager, Lien and Petta, Ioanna and Vandevyver, Sofie and Puim{\`e}ge, Leen and Mahieu, Tina and Ballegeer, Marlies and Van Hauwermeiren, Filip and Riccardi, Carlo and Vuylsteke, Marnik and Libert, Claude},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {INDUCED LEUCINE-ZIPPER,SPLENIC IMMUNE FUNCTIONS,X chromosome,SPRET/Ei,LPS,inflammation,Gilz,FEMALES,PROTEIN,SEPSIS,EXPRESSION,MOUSE STRAIN SPRET/EI,FACTOR-KAPPA-B,GLUCOCORTICOID-RECEPTOR,ALVEOLAR MACROPHAGES},
  language     = {eng},
  number       = {3},
  pages        = {456--470},
  title        = {LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome},
  url          = {http://dx.doi.org/10.1002/emmm.201201683},
  volume       = {5},
  year         = {2013},
}

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