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Monoallelic expression of the murine gene encoding Toll-like receptor 4

Nature Immunology volume 4, pages 464–470 (2003)Cite this article

Abstract

Defects in the gene encoding Toll-like receptor 4 (Tlr4) result in impaired responses to lipopolysaccharide (LPS), rendering mice sensitive to infections by Gram-negative bacteria. C3H/HeJ mice have a codominant allele with a mutation in Tlr4, which results in an intermediate response to LPS in F1 mice from crosses of responder and C3H/HeJ mice. Here we show that this intermediate response to LPS is due to monoallelic expression of Tlr4. Allele usage is maintained during clonal expansion, a situation that resembles allelic exclusion. In contrast, Tlr4 is deleted on the recessive C57BL/10ScCr allele and all cells from F1 mice from crosses of responder and C57BL/10ScCr mice express TLR4 protein. Thus, Tlr4 is an autosomal gene whose expression is regulated similarly to that of genes on the X chromosome.

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Figure 1: Expression of Tlr4 mRNA in spleen and bone marrow cells from B6 mice.
Figure 2: Flow cytometry analysis of CD14 expression in LPS-stimulated bone marrow granulocytes.
Figure 3: Expression of CD69 in LPS-stimulated B lymphocytes.
Figure 4: Kinetics of CD69 up-regulation in LPS-stimulated B lymphocytes.
Figure 5: Single-cell analysis of Tlr4 allele usage.
Figure 6: Expression of Tlr4 during B cell ontogeny.
Figure 7: RT-PCR analysis of Tlr4 allele usage during B cell ontogeny.

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Acknowledgements

We thank S. Vilarinho and M.T. Silva for encouragement; T. Pedron for technical help; O. Azougui, A. Peixoto, M. Monteiro and especially P. Pereira for discussions; and P. Pereira, A. O'Garra and D. Kioussis for critically reading the manuscript. J.P.P. was supported by fellowships from PRAXIS XXI (BD/15531/97), the Instituto Gulbenkian de Ciência and the Association pour la Recherche sur le Cancer.

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Authors and Affiliations

  1. Unité du Développement des Lymphocytes (CNRS URA 1961), Institut Pasteur, 25 Rue du Docteur Roux, Paris, France, 75015

    João Pedro Pereira, Robert Girard, Ana Cumano & Paulo Vieira

  2. Equipe Endotoxines (CNRS UMR-8619), Université Paris-Sud, Orsay, 91405, France

    Richard Chaby

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Correspondence to Paulo Vieira.

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Pereira, J., Girard, R., Chaby, R. et al. Monoallelic expression of the murine gene encoding Toll-like receptor 4. Nat Immunol 4, 464–470 (2003). https://doi.org/10.1038/ni917

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