| To simplify the analysis of asthma susceptibility genes located at human 5q23–35, we examined congenic mice that differed at the homologous chromosomal segment. We identified a Mendelian trait, T cell and Airway Phenotype Regulator (Tapr), that is genetically distinct from known cytokine genes, and that controls the development of airway hyperreactivity and T cell production of IL-4 and IL-13. Positional cloning revealed a novel gene family encoding T cell membrane proteins (Tim ), with conserved extracellular immunoglobulin and mucin-like domains, in which major sequence variants cosegregate completely with Tapr . The human homologue of TIM-1 is the hepatitis A virus (HAV) receptor, which may explain the inverse relationship between HAV infection and the development of atopy. |
