Transgenic mice expressing human toll-like receptor 4 (hTLR4)
TLR4 is the signaling receptor responsible for recognizing lipopolysaccharide (LPS), a major marker for gram-negative pathogens and a highly potent activator of the innate immune response. After activation of TLR4 in a variety of different cells like macrophages, granulocytes and dendritic cells, LPS triggers the release of a large spectrum of inflammatory mediators leading to an immune response. If inappropriately strong, this response might cumulate in endotoxin shock and death. Furthermore, by using transgenic mice expressing the human variant of TLR4, it has been shown that hTLR4 (but not mTLR4) is a direct target for nickel (Ni2+) and as a consequence plays a crucial role in the development of contact allergy. Mice expressing the human variant of TLR4 therefore provide an excellent animal model to be used in preclinical studies for the development of anti-inflammatory drugs based on interference with TLR4-mediated signaling.
Scientists from the Max-Plack-Institute for Immunobiology in Freiburg developed transgenic mice that express human toll-like receptor 4 (hTLR4) on a mTlr4-/- background. Mice were derived by pronuclear injection of fertilized eggs from the C57BL/10ScCr (Cr) mouse strain. These mice bear a natural deletion of the Tlr4 gene and are known to have an additional IL-12Rβ2 defect that was removed by backcrossing to the mTlr4-/-, Cr-progenitor strain C57BL/10ScN. Following strains that carry a hTlr4-transgene are available for licensing: