Cloning and expression analysis of the murine lymphotoxin beta gene.
Tumor necrosis factor alpha (TNF-alpha) and soluble lymphotoxin (LT) (also called LT-alpha or TNF-beta) are cytokines with similar biological activities that are encoded by related and closely linked genes. TNF-alpha, a mediator of the inflammatory response, exists in soluble and transmembrane forms. LT-alpha can be secreted or retained at the cell surface by binding to a 33-kDa transmembrane subunit, LT-beta. The recently cloned human LT-beta 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-alpha and LT-beta, whose physiological function is not yet clearly defined. We now report the sequence analysis of the genomic region and cDNA of murine LT-beta gene, which is closely associated with the TNF-alpha and LT-alpha genes within the murine major histocompatibility complex locus. Unlike the TNF-alpha, LT-alpha, and human LT-beta genes, which contain four exons, the murine LT-beta 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-beta in lymphoid and hematopoietic tissues. LT-beta transcription is maximal in the thymic medulla and in splenic white pulp. LT-beta mRNA is also detected in the skin and in specific regions of the brain. The LT-beta promoter region contains putative Ets-binding sites, suggesting that the expression of LT-beta may be regulated in part by Ets transcription factors whose pattern of lymphoid expression overlaps that of LT-beta.
Pokholok
D K
DK
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp. Frederick, MD 21702-1201.
Maroulakou
I G
IG
Kuprash
D V
DV
Alimzhanov
M B
MB
Kozlov
S V
SV
Novobrantseva
T I
TI
Turetskaya
R L
RL
Green
J E
JE
Nedospasov
S A
SA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics*; D053308:Lymphotoxin-beta; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; 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; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha