Allelic loss mapping and physical delineation of a region harboring a putative thymic lymphoma suppressor gene on mouse chromosome 12

Our previous allelic loss analasis of gamma-ray induced thymic lymphomas in F-1 hybrid and backcross mice between BALB/c and MSM strains mapped the Tl sr4 region exhibiting a high frequency of allelic loss (62%) to a 2.9 cM in terval between the markers D12Mit53 and D12Mit279 on mouse chromosome 12, T o narrow further the interval harboring a putative tumor suppressor gene, a high-density scan has been carried out for informative 361 thymic lymphoma s, Construction of a physical map of Tlsr4 with 3 YAC and 15 BAC clones and isolation of YAC- and BAC-derived polymorphic probes lead to fine allelic loss mapping. Three successive pola morphic sites within one BAC exhibit th e retention of both alleles in seven, one and four lymphomas, suggesting th at a common region of allelic loss for Tlsr4 exists within the BAC region. Pulsed-field gel electrophoresis of NotI digests of this and other clones d etermines that the commonly lost region is a 35 kb interval with a NotI sit e. NotI sites are frequently associated with coding regions, and our prelim inary sequencing has identified ESTs in the region. Thus, the present study facilitates the identification of genes in the Tlsr4 region that mould lea d to isolation of a novel tumor suppressor gene.