Characterization of the mouse lymphotoxin-beta gene.
Lymphotoxin-beta (LT-beta) is a member of the TNF family of ligands which when expressed with lymphotoxin-alpha (LT-alpha, i.e., the original LT or TNF-beta) forms a heteromeric complex with LT-alpha on the cell surface. The mouse gene structure was determined by both cDNA cloning and analysis of a genomic DNA fragment encompassing the TNF/LT locus in the H-2 region of chromosome 17. The mouse and human genomic structures were found to be similar in terms of location in the class III region of the MHC; however, the mouse gene lacks one intron found in most members of the family. Both the cDNA and the genomic sequences revealed an altered splice donor in the conventional intron 2 position, rendering it nonfunctional. The altered gene retains an open reading frame such that an additional 66 amino acids are inserted into the stalk region connecting the transmembrane domain with the receptor binding domain encoded by exon 4 in this type II membrane protein. Northern analysis showed that this gene is expressed predominantly in lymphoid organs. The outlining of the complete mouse TNF locus will further studies of the relationship between these genes and immune function.
Lawton
P
P
Department of Inflammation and Immunology, Biogen, Cambridge, MA 02142.
Nelson
J
J
Tizard
R
R
Browning
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D007438:Introns; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D009928:Organ Specificity; D012326:RNA Splicing; D016415:Sequence Alignment; D017385:Sequence Homology; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018076:DNA, Complementary; C505886:LTB protein, human; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha