Cloning and genomic characterization of LST1: a new gene in the human TNF region

Abstract

The leucocyte specific transcript - 1 (LST1) represents the human homolog of the mouse B144 transcript, encoded within the tumor necrosis factor (TNF) region of the human major histocompatibility complex class III interval. The gene is localized about 4 kilobases upstream of the lymphotoxin beta gene. It spans a polymorphic genomic region encompassing the microsatellites TNFd and TNFe in intron 3 and a polymorphic Pvu II restriction site 260 base pairs downstream of the polyadenylation signal. Isolation of a full-length cDNA clone revealed that LST1 codes for IFN-gamma-inducible 800 nt transcripts, which are present in lymphoid tissues, T cells, macrophages, and histiocyte cell lines. The cDNA contains three long open reading frames (ORF) with the most likely ORF encoding a transmembrane protein. Its close linkage to the TNF genes and pattern of expression point toward a possible role for LST1 in the immune response.

LST1/A Is a Myeloid Leukocyte-specific Transmembrane Adaptor Protein Recruiting Protein Tyrosine Phosphatases SHP-1 and SHP-2 to the Plasma Membrane

“…It revealed that LST1/A is substantially enriched in the spleen, peripheral blood monocytes, and granulocytes, as well as the cell lines of myeloid origin, indicating that LST1/A is expressed predominantly in the leukocytes of myeloid lineage. Although this conclusion is only in partial agreement with previously published studies (1,3,(5)(6)(7)(8), we consider our results reliable for several reasons. 1) We analyzed LST1/A expression profile in primary tissues and blood subpopulations, as well as in cell lines both at the protein and the mRNA levels and obtained a set of mutually supporting data.…”

“…ing results on the expression pattern of LST1 have been reported (1,3,5,7,8). Thus, we revisited this issue using a quantitative comparison of LST1/A expression levels in various cell subsets and tissues at both the mRNA and protein levels.…”

“…The human gene LST1 and its mouse homologue Lst1 (also known as B144) are located in the MHC class III locus, which is rich in immunologically important genes (1)(2)(3)(4). The human LST1 primary transcript has been reported to undergo extensive alternative splicing resulting in a large number of splice variants.…”

“…Several studies reported enrichment or specific expression of LST1 in leukocytes or leukocyte-rich tissues (1,3,7), whereas others indicated that the expression of LST1 is relatively ubiquitous (5,8). Moreover, it seems that production of particular isoforms could be differentially regulated, which further complicates expression analysis (5,9).…”

Discrimination of suballeles present at the TNFd microsatellite locus using induced heteroduplex analysis

“…2 Polymorphism has been described in intron 3 of the LST-1 gene, including two dinucleotide repeats termed TNFd and TNFe. 3 It has been reported that variability in TNFa production is associated with alleles at the TNFd locus. A strong correlation between inheritance of the TNFd3 allele and high TNFa production by leucocytes in vitro was shown.…”