Monoallelic expression of the murine gene encoding Toll-like receptor 4.
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.
Pereira
João Pedro
JP
Unité du Développement des Lymphocytes, CNRS URA 1961, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France.
Girard
Robert
R
Chaby
Richard
R
Cumano
Ana
A
Vieira
Paulo
P
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D016905:Gram-Negative Bacterial Infections / Q000235:genetics / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000235:genetics*; D013045:Species Specificity; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D004247:DNA