Gene profiling approach in the analysis of lymphotoxin and TNF deficiencies

Mice with combined lymphotoxin-alpha (LT alpha) and tumor necrosis factor ( TNF) deficiencies show defects hi the structure of peripheral lymphoid orga ns such as spleen, lymph nodes, and gut-associated lymphoid tissues. To ide ntify genes associated with this defective phenotype in spleen. we applied a gene profiling approach, including subtractive cloning and gene array hyb ridizations, to mice with combined TNF/LT deficiency. The differentially ex pressed genes identified by these techniques was then evaluated by Northern blot analysis for splenic expression ill knockout mice with single LT alph a or single TNF deficiency. Most of the genes detected in this analysis are directly or indirectly associated with disrupted LT and not TNF signaling.