Cloning and Expression Analysis of the Murine Lymphotoxin β Gene

Tumor necrosis factor α (TNF-α) and soluble lymphotoxin (LT) (also called LT-α or TNF-β) are cytokines with similar biological activities that are encoded by related and closely linked genes. TNF-α, a mediator of the inflammatory response, exists in soluble and transmembrane forms. LT-α can be secreted or retained at the cell surface by binding to a 33-kDa transmembrane subunit, LT-β. The recently cloned human LT-β gene encodes another TNF family member and is linked to the TNF/LT locus within the major histocompatibility complex locus. The cell surface LT is a heterotrimer consisting of LT-α and LT-β, whose physiological function is not yet clearly defined. We now report the sequence analysis of the genomic region and cDNA of murine LT-β gene, which is closely associated with the TNF-α and LT-α genes within the murine major histocompatibility complex locus. Unlike the TNF-α, LT-α, and human LT-β genes, which contain four exons, the murine LT-β contains three exons and encodes a 244-amino acid polypeptide with a 66-amino acid insert that is absent from the human homologue. In situ hybridization demonstrates constitutive expression of LT-β in lymphoid and hematopoietic tissues. LT-β transcription is maximal in the thymic medulla and in splenic white pulp. LT-β mRNA is also detected in the skin and in specific regions of the brain. The LT-β promoter region contains putative Ets-binding sites, suggesting that the expression of LT-β may be regulated in part by Ets transcription factors whose pattern of lymphoid expression overlaps that of LT-β.