斑马鱼尾加压素Ⅱ受体基因组织表达的研究

尾加压素Ⅱ受体(UrotensinⅡreceptor,UT)是一种7次跨膜G蛋白偶联受体,是目前发现的具有最强收缩血管作用的尾加压素Ⅱ的特异性受体。斑马鱼中存在4种不同的UT-like基因(uts2r1,uts2r2,uts2r3和uts2r4),分别位于斑马鱼4条不同染色体上。这4种uts2r基因核苷酸序列各不相同,uts2r1位于3号染色体上,其与12号染色体上的uts2r2基因蛋白序列相似度最高为47%,与6号染色体上的uts2r3和16号染色体上的uts2r4蛋白相似度分别是41.6%和33%。通过设计特异引物检测每种uts2r基因在斑马鱼成鱼各组织中的表达情况,结果显示3号染色体上的uts2r1基因在肾脏中表达量最高,6号染色体上的uts2r2基因在脊髓中表达量最高,12号染色体上的uts2r3基因在心脏中表达量最高,而16号染色体上的uts2r4基因在背肌中表达量最高。     

Chromosomal localization of muscle nicotinic acetylcholine receptor genes in the mouse

The chromosomal localization of the genes encoding the four subunits of muscle nicotinic receptor was determined by analyzing restriction fragment length polymorphisms between two mouse species Mus musculus domesticus (DBA/2) and Mus spretus (SPE). Analysis of the progeny of the interspecies mouse backcross (DBA/2 X SPE) X DBA/2 showed that the alpha-subunit gene cosegregates with the alpha-cardiac actin gene on chromosome 17, that the beta-subunit gene is located on chromosome 11, and that the gamma- and delta-subunit genes cosegregate and are located on chromosome 1.     

Trans-activator gene of HTLV-II induces IL-2 receptor and IL-2 cellular gene expression

The human T-lymphotropic viruses types I and II (HTLV-I and -II) have been etiologically linked with certain T-cell leukemias and lymphomas that characteristically display membrane receptors for interleukin-2. The relation of these viruses to this growth factor receptor has remained unexplained. It is demonstrated here that introduction of the trans-activator (tat) gene of HTLV-II into the Jurkat T-lymphoid cell line results in the induction of both interleukin-2 receptor and interleukin-2 gene expression. The coexpression of these cellular genes may play a role in the altering T-cell growth following retroviral infection.     

Regulation of expression of the interleukin-2 receptor on hematopoietic cells by interleukin-3

Remarkable similarities in the intracellular and genetic events occur when lymphoid and hematopoietic cells are exposed to their specific growth factors. The interleukin-2 (IL-2) receptor, whose cell-surface expression is an absolute requirement for the growth and differentiation of lymphoid cells, was detected on various nonlymphoid hematopoietic cell types in this study. Cell lines consisting either of granulocyte-macrophage precursors or mast cells, which are dependent on interleukin-3 (IL-3) for their growth, expressed high levels of the IL-2 receptor on their surface. Analysis of the binding characteristics of these receptors with 125I-labeled recombinant IL-2 revealed that only receptors with low affinity for IL-2 were present on these cells. Addition of purified recombinant IL-3 to these cell lines led to an increase in IL-2 receptor gene expression within 1 hour in isolated nuclei. This IL-3--induced increase in the number of IL-2 receptors on the cell surface is maximal within 24 hours. Addition of 10,000 units of IL-2 to these cells had no apparent effect on their growth or differentiation. The presence of the receptor with only low affinity for IL-2 on hematopoietic cells and the regulation by IL-3 suggest that this receptor is involved in some important metabolic event in hematopoiesis.     

Gene for T-cell growth factor: location on human chromosome 4q and feline chromosome B1

T-cell growth factor (TCGF) or interleukin-2 (IL-2), an immunoregulatory lymphokine, is produced by lectin- or antigen-activated mature T lymphocytes and in a constitutive manner by certain T-cell lymphoma cell lines. By means of a molecular clone of human TCGF and DNA extracted from a panel of somatic cell hybrids (rodent cells X normal human lymphocytes), the TCGF structural gene was identified on human chromosome 4. In situ hybridization of the TCGF clone to human chromosomes resulted in significant labeling of the midportion of the long arm of chromosome 4, indicating that the TCGF gene was located at band q26-28. Genomic DNA from a panel of hybrids prepared with HUT-102 B2 cells was examined with the same molecular clone. In this clone of cells, which produces human T-cell leukemia virus, the TCGF gene was also located on chromosome 4 and was apparently not rearranged. The homologous TCGF locus in the domestic cat was assigned to chromosome B1 by using a somatic cell hybrid panel that segregates cat chromosomes. Linkage studies as well as high-resolution G-trypsin banding indicate that this feline chromosome is partially homologous to human chromosome 4.     

The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C

The Prader-Willi syndrome is a congenital disease that is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15. This region contains a small nucleolar RNA (snoRNA), HBII-52, that exhibits sequence complementarity to the alternatively spliced exon Vb of the serotonin receptor 5-HT(2C)R. We found that HBII-52 regulates alternative splicing of 5-HT(2C)R by binding to a silencing element in exon Vb. Prader-Willi syndrome patients do not express HBII-52. They have different 5-HT(2C)R messenger RNA (mRNA) isoforms than healthy individuals. Our results show that a snoRNA regulates the processing of an mRNA expressed from a gene located on a different chromosome, and the results indicate that a defect in pre-mRNA processing contributes to the Prader-Willi syndrome.     

Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias

Mouse lymphoma cells were hybridized with two human acute T-cell leukemias with a t(11;14) (p13;q11) translocation and the segregated hybrids were examined for the presence of the DNA segments coding for the constant (C) and the variable (V) regions of the alpha chain (C alpha and V alpha) of the T-cell receptor. The C alpha segment was translocated to the involved chromosome 11 (11p+) while the V alpha segment remained on the involved chromosome 14 (14q-). The data indicate that the locus for the alpha chain of the T-cell receptor is split by the chromosomal breakpoint between the V alpha and the C alpha gene segments, and that the V alpha segments are proximal to the C alpha segment within chromosome band 14q11.2.     

The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor

The neu oncogene, identified in ethylnitrosourea-induced rat neuroglioblastomas, had strong homology with the erbB gene that encodes the epidermal growth factor receptor. This homology was limited to the region of erbB encoding the tyrosine kinase domain. It was concluded that the neu gene is a distinct novel gene, as it is not coamplified with sequences encoding the EGF receptor in the genome of the A431 tumor line and it maps to human chromosome 17.     

A genome-wide association study identifies IL23R as an inflammatory bowel disease gene

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.     

Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells

The T-cell receptor is formed by two chains, alpha and beta, for which specific clones were recently obtained. In this report the gene for the beta chain of the human T-cell receptor was located on the long arm of chromosome 7, band q35, by means of in situ hybridization. This chromosome region in T cells is unusually prone to develop breaks in vivo, perhaps reflecting instability generated by somatic rearrangement of T-cell receptor genes during normal differentiation in this cell lineage.     

The interleukin-2 T-cell system: a new cell growth model

Synchronized interleukin-2 receptor-positive T cells, homogeneous immunoaffinity-purified interleukin-2, and a monoclonal antibody to interleukin-2 receptors were used to show that only three factors are critical for T-cell cycle progression: interleukin-2 concentration, interleukin-2 receptor density, and the duration of the interleukin-2 receptor interaction. Since the proliferative characteristics of T cells are identical to those of both prokaryotic and all other eukaryotic cells, these findings provide a new model that accounts fully for the variables that determine cell cycle progression.     

A common mechanism of chromosomal translocation in T- and B-cell neoplasia

The chromosomal breakpoint involved in the t(8;14)(q24;q11) chromosome translocation in the SKW-3 cell line, which directly involves the 3' flanking region of the c-myc gene, was cloned and sequenced. The breakpoint on chromosome 8 mapped to a position 3 kb 3' of c-myc while the chromosome 14 breakpoint occurred 36 kb 5' of the gene for the constant region of the alpha chain of the T-cell receptor (TCR). The translocation resulted in a precise rearrangement of sequences on chromosome 8 and what appears to be a functional J alpha segment on chromosome 14. Signal sequences for V-J joining occurred at the breakpoint positions on both chromosomes 14 and 8, suggesting that the translocation occurs during TCR gene rearrangement and that it is catalyzed by the enzymatic systems involved in V-J joining reactions. The involvement of c-myc in the translocation and the association of joining signals at the breakpoints provides a parallel to the situation observed in the translocations involving c-myc and the immunoglobulin loci in B-cell neoplasms and suggests that common mechanisms of translocation and oncogene deregulation are involved in B- and T-cell malignancies.     

1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone

The hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], at picomolar concentrations, inhibited the growth-promoting lymphokine interleukin-2, which is produced by human T lymphocytes activated in vitro by the mitogen phytohemagglutinin. Other metabolites of vitamin D3 were less effective than 1,25(OH)2D3 in suppressing interleukin-2; their order of potency corresponded to their respective affinity for the 1,25(OH)2D3 receptor, suggesting that the effect on interleukin-2 was mediated by this specific receptor. The proliferation of mitogen-activated lymphocytes was also inhibited by 1,25(OH)2D3. This effect of the hormone became more pronounced at later stages of the culture. These findings demonstrate that 1,25(OH)2D3 is an immunoregulatory hormone.