Kristin Stephan, B.S.,
Physiology & Molecular Biology,
Marshall University
Huntington, WV
Ph.D. Student in Immunology
E-mail: kristin.stephan@tufts.edu

The innate immune response is governed in part by the family of toll-like receptors (TLRs). Among them, Tlr9 is a receptor for unmethylated CpG motifs present at a high frequency in bacterial but not vertebrate DNA. By recognizing the CpG DNA, Tlr9 signals the presence of microbial infection. Does Tlr9 signal alone or it is being helped by other molecules? I am trying to answer this question using a forward genetics approach in the wild-derived mouse strain MOLF/Ei. Unlike other wild-derived strains, these mice are non-responsive to CpG. Linkage analysis on a panel of intercross F2(MOLF x C57Bl/6J) mice shows the CpG non-response in MOLF/Ei mice is not linked to Tlr9 but to another locus. Based on this discovery, I will identify the mutation(s) responsible for non-response to CpG in MOLF/Ei mice by positional cloning and study the functional properties of a new co-receptor to CpG.