Limits of a deletion spanning Tlr4 in C57BL/10ScCr mice

Proceeding from our observation that LPS-unresponsive mice of the strain C5 7BL/10ScCr mice fail to express the Tlr4 gene [Poltorak A, He X. Smirnova I et nl. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282. 2085], we have defined the exact limits o f a deletion encompassing Tlr4 in the C57BL/10ScCr genome. The deletion rem oves 74723 bp of DNA, with reference to the control strain 129/J (from whic h the complete sequence of the Tlr4 locus was obtained). There is no insert ed element, and no re-arrangement of the chromosome (e.g. inversion or tran slocation) in the immediate region of Tlr4; the deletion removes only one r ecognizable gene. Hence, other immunological anomalies that have been ident ified in C57BL/10ScCr mice (a nonhealing phenotype in Leishmania inoculatio n and failure to produce interferon-gamma in response to numerous microbial infections) must be ascribed to one of two causes. Mutation(s) at other lo ci may be responsible for these defects. Alternatively, Tlr4 locus deletion may have phenotypic consequences that exceed the well known blockade of LP S signal transduction.