Variant TLR4 nucleic acid and uses thereof

An isolated and purified nucleic acid molecule comprising a human nucleic acid segment encoding a variant TLR4, or a biologically active fragment thereof.

An expression cassette comprising a promoter operably linked to a human DNA segment encoding a variant TLR4, or a biologically active fragment thereof.

A method of identifying a human at risk of, or having, an indication associated with altered innate immunity, comprising:

• a) contacting an amount of DNA obtained from a human physiological sample with an amount of at least one TLR4-specific oligonucleotide under conditions effective to amplify the DNA so as to yield amplified DNA;
• and
• b) detecting or determining whether the amplified DNA encodes at least a portion of a variant TLR4.

Isolated, variant human TLR4 polypeptide, or a biologically active fragment thereof.

A method to identify an agent that alters TLR4 activity, comprising:

• a) contacting a mammalian cell which expresses TLR4 with the agent;
• and
• b) detecting or determining whether the agent alters TLR4 activity.

A method to alter TLR4 activity, comprising:

• contacting a mammalian cell with an agent effective to alter TLR4 activity.

A method to detect a polymorphism in a human TLR4 gene, comprising:

• detecting or determining whether a nucleic acid sample obtained from a human comprises nucleic acid encoding variant TLR4.

A transgenic mouse whose cells comprise a chimeric DNA sequence, wherein the chimeric DNA sequence comprises a DNA segment encoding human TLR4, wherein the chimeric DNA sequence is integrated into the genome of the cells of the mouse, and wherein the DNA segment is expressed in the transgenic mouse so as to result in the transgenic mouse exhibiting altered innate immunity relative to a corresponding nontransgenic mouse.