Transgenic male mice express human TLR4 (toll-like receptor 4) and, the TLR4 co-receptor, human LY96 (MD-2). Transgenic female mice express human TLR4 only. TLR4 is a member of the Toll-like receptor family and is involved in the recognition of lipopolysaccharide (LPS) and the activation of innate immunity. LPS is produced by gram-negative bacteria. Acylation of lipid A, the bioactive component of LPS, is altered, in some organisms, by temperature and affects susceptibility of the host to Gram negative bacteria. Yersinia pestis cultured at 37 C (representative of mammalian, rather than insect, hosts) results in hypo-acylation of lipid A; the tetra-acylated lipid A reduces the LPS stimulatory response in humans and blunts inflammatory cytokine production, but does not alter murine response to LPS. When null alleles of Tlr4 and Ly96 are bred into TLR4/MD-2 transgenic males, mouse susceptibility to Y. pestis models the human response. This strain may be useful for studying selective immune evasion in bacterial pathogens.

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 Transgenic male mice express human TLR4 (toll-like receptor 4) and, the TLR4 co-receptor, human LY96 (MD-2). This strain may be useful for studying selective immune evasion in bacterial pathogens.

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