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US 7,029,861 B1Granted
LPS-response gene compositions and methods
AssigneeBoard of Regents, The University of Texas System
InventorsBruce A. Beutler, Alexander Poltorak
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Abstract
The present invention describes a mutant TLR-4 in mice that does not recognize endotoxin and therefore does not stimulate the secretion of TNF from macrophages. Methods of detecting the mutation are provided; as are methods screening for drugs that may stimulate TNF production. Finally methods of incorporating and expressing the mutant TLR-4 genes into a host cell are contemplated.
Claims26
A method of screening for modulators of a lipopolysaccharide mediated response comprising the steps of:
- a) obtaining a cell expressing a TLR-4 polypeptide, wherein the TLR-4 polypeptide has the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:98 or SEQ ID NO:99, or is encoded by a nucleic acid sequence comprising SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:46, SEQ ID NO:47 or SEQ ID NO:48;
- b) measuring a lipopolysaccharide mediated response mediated by the TLR-4 polypeptide;
- c) contacting the TLR-4 polypeptide with a putative modulator;
- d) assaying for a change in the lipopolysaccharide mediated response;
- and
- e) comparing the lipopolysaccharide mediated responses mediated by the TLR-4 polypeptide obtained in steps b) and d) above
- wherein a difference in the lipopolysaccharide mediated responses indicates that the putative modulator is a modulator of a lipopolysaccharide mediated response.
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Dependencies are inferred from the claim text.