Physical mapping of the autoimmune disease susceptibility locus, Bphs: co-localization with a cluster of genes from the TNF receptor superfamily on mouse Chromosome 6

An important approach to understanding complex diseases is to reduce them i nto well-characterized subphenotypes that are under monogenic control. One such example is Bordetella pertussis toxin-induced histamine sensitization in mice, a subphenotype of experimental allergic encephalomyelitis and expe rimental allergic orchitis. This subphenotype is controlled by a single loc us, Bphs, previously mapped to a 33 cM region on mouse Chromosome (Chr) 6. We achieved considerable reduction of this candidate region and constructed a YAC contig across the refined interval. Our results demonstrate that Bph s is located between D6Mit151 and a newly developed marker, EC108RR, a regi on containing a small cluster of genes belonging to the TNF receptor superf amily. Sequence and quantitative analysis of the candidate gene, tumor necr osis factor receptor 1 (Tnfr1, p55), indicates that it is unlikely to be Bp hs. However, the location of Bphs, together with physiologic effects it sha res with Tnfr1 activation, suggest that Bphs may prove to be another member of the TNF receptor superfamily.