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PubMed2004

The endothelin receptor antagonist ameliorates the hypertensive phenotypes of transgenic hypertensive mice with renin-angiotensin genes and discloses roles of organ specific activation of endothelin system in transgenic mice.

Endothelin (ET)-1 and ET-2 are potent vasoconstrictor peptides with mitogenic activity. In this study, we investigated roles of ET system in renin-angiotensin system (RAS)-mediated hypertension, using transgenic hypertensive mice (THM) with over-expression of both human renin and angiotensinogen genes. In the first step, it was revealed that expression of ET system was locally enhanced, i.e. increases in cardiac preproET-1 mRNA and renal preproET-2 mRNA in THM, compared with the control (wild type) mice. In the next step, we studied the chronic effects of an ET antagonist (SB209670) on THM. Blood pressure (BP) in THM was significantly higher than that in the normal mice during the investigation. However, in the later phase of the study, from 12 to 20 weeks of treatment, THM receiving SB 209670 showed significantly lower BP than that in THM receiving saline. SB 209670 treatment for 20 weeks significantly attenuated phenotypes of cardiac hypertrophy, vascular wall thickening and hypertensive nephropathy observed in THM, suggesting that the ETA/B receptor antagonist is also effective even in the extraordinarily activated RAS condition. These findings suggest that organ specifically activated ET system in THM develops the phenotypes, hypertension, cardiac hypertrophy, and hypertensive nephropathy.

Animals↗
PubMed2005

Midkine regulates pleiotrophin organ-specific gene expression: evidence for transcriptional regulation and functional redundancy within the pleiotrophin/midkine developmental gene family.

Midkine (MK) and the highly related cytokine pleiotrophin (PTN) constitute the PTN/MK developmental gene family. The Mk and Ptn genes are essential for normal development of the catecholamine and renin-angiotensin pathways and the synthesis of different collagens. It is not known whether the Ptn and Mk genes regulate each other or whether PTN and MK are functionally redundant in development. We have now compared the levels of expression of Ptn and Mk in genetically deficient Mk -/- and Ptn -/- mice and found highly significant increases in Ptn gene expression in spinal cord, dorsal root ganglia, eye, heart, aorta, bladder, and urethra, but not in brain, bone marrow, testis, and lung of Mk -/- mice compared with wild type mice; a remarkable approximately 230-fold increase in Ptn expression levels was found in heart of Mk -/- mice and highly significant but lesser increases were found in six other organs. Differences in levels of Mk gene expression in Ptn -/- mice could not be detected in any of the organs tested. The data demonstrate that MK regulates Ptn gene expression with a high degree of organ specificity, suggesting that Ptn gene expression follows Mk gene expression in development, that the increase in Ptn gene expression is compensatory for the absence of MK in Mk -/- mice, that PTN and MK share a high degree of functional redundancy, and that MK may be very important in the development of heart in mouse.

Animals↗
PubMed1992

[Parameters of organ-specific and non-specific autoimmunity in patients with Basedow's disease and Basedow's ophthalmopathy. Changes induced by IVIG treatment].

The aim of this study was to evaluate the variations of thyroid autoantibodies titre in a group of 15 patients affected with "Graves' disease" (G. D.) during the treatment with antithyroid drug (ATD) and "high dose intravenous immunoglobulin" (IVIG) for "Graves' ophthalmopathy". Before the starting of treatment thyroglobulin antibodies (TgAb) were positive in 10/15 patients, microsomal antibodies (MAb) were positive in 13/15 patients and TRAb were positive in 5/9 patients. At the end of treatment TgAb titre was decreased or negative in 7/10 patients, MAb titre was decreased or negative in 7/13 patients, TRAb titre was diminished or negativized in 5/5 patients. Anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were positive in 3/15 and 3/15 patients before the treatment and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA)m anti-mitochondrial antibodies (AMA) and rheumatoid factors were negative in all the patients. Also in the 3 patients not treated with ATD we have observed a reduction or a negativization of circulating thyroid autoantibodies. In conclusion these data suggest that the reduction of thyroid and non organ specific autoantibodies might be due to a stable immunosuppressive action of IVIG treatment in patients with Graves' disease.

Autoantibodies↗
PubMed2004

Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity.

Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire-dependent tolerance mechanisms are susceptible to the quantitative genetic changes thought to underlie more common autoimmune diseases. In mice with a targeted mutation, complete loss of Aire abolished expression of an insulin promoter transgene in thymic epithelium, but had no effect in pancreatic islets or the testes. Loss of one copy of Aire diminished thymic expression of the endogenous insulin gene and the transgene, resulting in a 300% increase in islet-reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice, and dramatically increased progression to diabetes. Thymic deletion induced by antigen under control of the thyroglobulin promoter was abolished in Aire homozygotes and less efficient in heterozygotes, providing an explanation for thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on thymic deletion to antigen controlled by a systemic H-2K promoter. The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity.

Animals↗
PubMed1969

Organ-specific estrogen-induced RNA synthesis resolved by DNA-RNA hybridization in the domestic fowl.

In the domestic fowl and other oviparous vertebrates, estrogens induce hepatic synthesis of yolk proteins. The oviduct also increases in size and produces ovalbumin when estrogens are administered. DNA-RNA hybridization assays indicate that within 105 minutes following treatment with estrone the liver of immature pullets contains most, if not all, of the liver RNA species that are present in the livers of the laying hen. Because of limitations of the nucleic acid hybridization technique, which remain to be clearly defined, it is not known whether the hepatic RNA populations in estrone-treated pullets and laying hens are completely homologous or differ in some important way. The results indicate that the genomic response in the avian liver to exogenous estrone is "normal" (relative to the laying hen) and further suggest that the hepatic response to estrogen is primarily pertinent to vitellinogenesis.DNA-RNA hybridization assays on total RNA also indicate that estrogen-induced RNA species in the liver are not homologous to estrogen-evoked RNA species of the oviduct. Therefore, in these two target organs estrogen-evoked RNA synthesis appears to be in part organ-specific. These data indicate that the specificity of hormone action can be explained in part on the basis of induced synthesis of specific RNA molecules. Whether these alterations in transcription are due to indirect hormonal action or are the result of a primary action of estrogens or estrogen-binding site complexes on the genome and/or its repressors remains a basic question.

Animals↗
PubMed1985

N-Nitroso-N-methylurea initiation in multiple tissues for organ-specific tumor promotion in rats by phenobarbital.

Effects of phenobarbital [(PB) CAS: 50-06-6], a systemic tumor promoter, on carcinogenesis initiated by the broad-spectrum carcinogen N-nitroso-N-methylurea [(NMU) CAS: 684-93-5] were investigated in F344/NCr rats. Single and divided doses of NMU were evaluated for this purpose in 4-week-old rats of both sexes. Rats received iv injections of either 0.2 mmol NMU/kg (body wt) once or 0.05 mmol NMU/kg (body wt) for 4 weeks (1 injection/wk), followed by or concurrently with PB (0.05% in drinking water) that was continued until the termination of the experiment. Half the rats were killed at 52 weeks and survivors at 80 weeks. At 52 weeks, PB given subsequent to NMU or concurrently with divided doses of NMU significantly enhanced the incidence of thyroid follicular tumors only in male rats. This sex difference in thyroid tumorigenesis was somewhat less pronounced in animals killed at 80 weeks. Only 1 liver cell adenoma occurred in males and none in females given NMU alone. PB given concurrently with divided doses of NMU enhanced the yield of hepatocellular foci/cm2 but had no significant effect on hepatic tumor development. Subsequent exposure to PB, however, significantly promoted hepatocarcinogenesis in rats of both sexes given NMU in divided doses; 50% of males and 40% of females given NMU (0.05 mmol/kg, administered four times) followed by PB had hepatocellular adenomas and carcinomas by 80 weeks. PB did not affect the incidence of any other kind of neoplasms seen in NMU-initiated or control rats. These lesions included squamous cell neoplasms of the skin, oropharynx, and forestomach; nonsquamous epithelial tumors of mammary gland, pituitary body, intestinal mucosa, and urinary bladder; tumors of the central and peripheral nervous system; and mesenchymal tumors of the kidney. A sequence of multiple low doses of NMU appeared to be a convenient and useful systemic, multitissue, tumor-initiation regimen for systematic investigation of organ-specific tumor promotion in rats.

Animals↗
PubMed2004

Spontaneous organ-specific Th2-mediated autoimmunity in TCR transgenic mice.

CD4(+) T cells that lead to autoimmune gastritis (AIG) in BALB/c mice are either Th1 or Th2 cells. To test whether the phenotype of disease is related to the particular TCR expressed by the pathogenic cell, we have generated several lines of TCR transgenic mice using receptors cloned from pathogenic Th1 or Th2 cells. We previously described spontaneous inflammatory AIG in A23 mice, caused by the transgenic expression of the TCR from a Th1 clone, TXA23. In this study we describe the generation of A51 mouse lines, transgenic for the TCR of a CD4(+) self-reactive Th2 clone, TXA51. A proportion of A51 mice spontaneously develop AIG by 10 wk of age, with a disease characterized by eosinophilic infiltration of the gastric mucosa and Th2 differentiation of transgenic T cells in the gastric lymph node. The Th2 phenotype of this autoimmune response seems to be related to a low availability of MHC class II-self peptide complexes. This in vivo model of spontaneous Th2-mediated, organ-specific autoimmunity provides a unique example in which the clonotypic TCR conveys the Th2 disease phenotype.

Adoptive Transfer↗
PubMed2005

Organ-specific and age-dependent expression of insulin-like growth factor-I (IGF-I) mRNA variants: IGF-IA and IB mRNAs in the mouse.

Insulin-like growth factor-I (IGF-I) gene generates several IGF-I mRNA variants by alternative splicing. Two promoters are present in mouse IGF-I gene. Each promoter encodes two IGF-I mRNA variants (IGF-IA and IGF-IB mRNAs). Variants differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain-coding region. Functional differences among IGF-I mRNAs, and regulatory mechanisms for alternative splicing of IGF-I mRNA are not yet known. We analyzed the expression of mouse IGF-IA and IGF-IB mRNAs using SYBR Green real-time RT-PCR. In the liver, IGF-I mRNA expression increased from 10 days of age to 45 days. In the uterus and ovary, IGF-I mRNA expression increased from 21 days of age, and then decreased at 45 days. In the kidney, IGF-I mRNA expression decreased from 10 days of age. IGF-IA mRNA levels were higher than IGF-IB mRNA levels in all organs examined. Estradiol-17beta (E2) treatment in ovariectomized mice increased uterine IGF-IA and IGF-IB mRNA levels from 3 hr after injection, and highest levels for both mRNAs were detected at 6 hr, and relative increase was greater for IGF-IB mRNA than for IGF-IA mRNA. These results suggest that expression of IGF-I mRNA variants is regulated in organ-specific and age-dependent manners, and estrogen is involved in the change of IGF-I mRNA variant expression.

Age Factors↗
PubMed2000

Plasmodium chabaudi-infected erythrocytes adhere to CD36 and bind to microvascular endothelial cells in an organ-specific way.

Adherence of erythrocytes infected with Plasmodium falciparum to microvascular endothelial cells (sequestration) is considered to play an important role in parasite virulence and pathogenesis. However, the real importance of sequestration for infection and disease has never been fully assessed. The absence of an appropriate in vivo model for sequestration has been a major barrier. We have examined the rodent malaria parasite Plasmodium chabaudi chabaudi AS in mice as a potential model. Erythrocytes infected with this parasite adhere in vitro to purified CD36, a critical endothelium receptor for binding P. falciparum-infected erythrocytes. P. c. chabaudi-infected erythrocytes adhere in vitro to endothelial cells in a gamma interferon-dependent manner, suggesting the involvement of additional adhesion molecules in the binding process, as is also the case with P. falciparum-infected cells. Furthermore, plasma or sera from infected and hyperimmune mice, respectively, have the ability to block binding of infected erythrocytes to endothelial cells. In vivo, erythrocytes containing mature P. c. chabaudi parasites are sequestered from the peripheral circulation. Sequestration is organ specific, occurring primarily in the liver, although intimate contact between infected erythrocytes and endothelial cells is also observed in the spleen and brain. The results are discussed in the context of the use of this model to study (i) the relationship between endothelial cell activation and the level of sequestration and (ii) the primary function of sequestration in malaria infection.

Animals↗
PubMed1994

Toxicity of neomycin on enzyme activities of kidney and duodenal mucosa in vivo: organ specificity and species difference between rats and mice.

Inhibitory effects of neomycin administration (10-80 mg/kg body weight/day, s.c. for 7 days) on several enzyme activities of kidney and duodenal mucosa were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase activity was inhibited by neomycin in a dose-dependent manner, while microsomal Mg(2+)-Na(+)-K(+)-ATPase activity and cytosol carbonic anhydrase (CA) activity were inhibited only by larger doses. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were also inhibited only by larger doses. Serum urea nitrogen (UN) concentration and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were increased in a dose-dependent manner. In ddY and C57black mice, however, all enzyme activities in kidney and duodenal mucosa were almost unaffected by any dose of neomycin and showed no changes in serum UN concentration and urinary NAG activity except for ddY mice in which NAG activity was only increased by the largest dose of neomycin. In light microscopic analysis, 80 mg neomycin/kg produced necrosis in the greater part of rat proximal tubuli with no changes in duodenal brush border. On the other hand, no histological changes were produced in the renal cortex or duodenal mucosa of mice by any dosage. In conclusion, there are organ-specific and species differences in the effects of neomycin between rats and mice.

Acetylglucosaminidase↗
PubMed1996

Biphasic, organ-specific, and strain-specific accumulation of platelets induced in mice by a lipopolysaccharide from Escherichia coli and its possible involvement in shock.

Platelets contain a large amount of 5-hydroxytryptamine (5HT, serotonin). Intravenous injection into BALB/c mice of a Boivin's preparation of lipopolysaccharide (LPS) from Escherichia coli induced rapid 5HT accumulation in the lung (within 5 min) and slow 5HT accumulation in the liver (2 to 5 h later). The rapid response required high doses of LPS (more than 0.1 mg/kg). On the basis of 5HT measurements, 70% or more of the platelets which disappeared from the blood appeared to have accumulated rapidly in the lung, and a large number of platelets were found there by electron microscopy. A shock, which was manifested by crawling, convulsion, or prostration, followed shortly after the rapid accumulation of 5HT in the lung. On the other hand, the slow accumulation of 5HT in the liver could be induced by much lower doses of LPS (1 microg/kg or less), even when given by intraperitoneal injection. This 5HT accumulation appears to be a reflection of platelet accumulation in the liver (Y. Endo and M. Nakamura, Br. J. Pharmacol. 105:613-619, 1992). The combination of a low dose of LPS with D-galactosamine amplified the hepatic accumulation of 5HT, and the mice developed a severe hepatic congestion resulting in death. The rapid response was not induced at all in C3H/HeN mice. These results and comparison with other LPS preparations indicate that some component(s) of LPS from E. coli induces a biphasic, organ-specific and strain-specific accumulation of platelets, and it is proposed that this effect is involved in the development of shock.

Animals↗
PubMed2006

Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development.

DNA methylation and histone methylation are two key epigenetic modifications that help govern heterochromatin dynamics. The roles for these chromatin-modifying activities in directing tissue-specific development remain largely unknown. To address this issue, we examined the roles of DNA methyltransferase 1 (Dnmt1) and the H3K9 histone methyltransferase Suv39h1 in zebra fish development. Knockdown of Dnmt1 in zebra fish embryos caused defects in terminal differentiation of the intestine, exocrine pancreas, and retina. Interestingly, not all tissues required Dnmt1, as differentiation of the liver and endocrine pancreas appeared normal. Proper differentiation depended on Dnmt1 catalytic activity, as Dnmt1 morphants could be rescued by active zebra fish or human DNMT1 but not by catalytically inactive derivatives. Dnmt1 morphants exhibited dramatic reductions of both genomic cytosine methylation and genome-wide H3K9 trimethyl levels, leading us to investigate the overlap of in vivo functions of Dnmt1 and Suv39h1. Embryos lacking Suv39h1 had organ-specific terminal differentiation defects that produced largely phenocopies of Dnmt1 morphants but retained wild-type levels of DNA methylation. Remarkably, suv39h1 overexpression rescued markers of terminal differentiation in Dnmt1 morphants. Our results suggest that Dnmt1 activity helps direct histone methylation by Suv39h1 and that, together, Dnmt1 and Suv39h1 help guide the terminal differentiation of particular tissues.

Animals↗
PubMedDate not supplied

Regulation of tumor cell growth at organ-specific metastases.

The hallmark of malignant neoplasms is their ability to spread beyond the site of origin and produce metastases in distant organs. This nonrandom process depends on the interaction of specific tumor cells with a compatible milieu provided by a particular organ microenvironment; the molecular basis of which is under intense investigation. Recent analysis of human colon carcinoma (HCC) cells obtained from surgical specimens and implanted into athymic nude mice suggested that whereas nonmetastatic and highly metastatic cells can grow at local sites, growth per se in the secondary organ-specific site was associated only with high-metastatic HCC cells. These cells also respond in a specific manner to physiological mitogenic signals produced by damaged normal tissues. This article addresses the biological and molecular evidence supporting the hypothesis that organ-derived, perhaps, organ-specific, paracrine growth factors stimulate the growth of receptive malignant cells that possess the appropriate receptors.

Animals↗
PubMed2006

Tamoxifen: important considerations of a multi-functional compound with organ-specific properties.

Tamoxifen remains a frontline treatment for hormone-responsive breast cancer despite its use being associated with a 2-7-fold elevated risk of developing endometrial carcinoma. Several groups have investigated whether tamoxifen induces DNA-damaging (genotoxic) versus non-genotoxic mechanisms. Some studies point to the presence of tamoxifen-DNA adducts while others suggest otherwise. In many of these studies, the histological sub-type has not been considered; as type 1 carcinomas are associated with PTEN and KRAS2 mutations whereas type 2 carcinomas exhibit TP53 and ERBB-2 mutations, the absence of this information makes comparisons between such independent investigations difficult. An examination of the sub-types of endometrial carcinoma points to histological and mechanistic distinctions between sporadic and tamoxifen-associated disease; this could suggest differing aetiologies. On this basis, we propose a dual mechanism of action highlighted by the different patterns of endometrial carcinoma sub-types. Tamoxifen may initially be pro-oestrogenic in the endometrium giving rise to elevated type 1 endometrioid carcinoma occurrence whereas after long-term use, there is an increase of type 2 disease or malignant mixed mullerian tumours associated with a hormone-independent mechanism of action. Despite these associated risk factors, and the introduction of new selective oestrogen receptor modulators (SERMs), we suggest that the organ-specific pleiotrophic effects of tamoxifen mean that this effective therapeutic agent for breast cancer will continue to have significant usage. The focus of future research should concentrate on the different aetiologies of tamoxifen-associated endometrial carcinomas while efforts continue to develop future SERMs.

Breast Neoplasms↗
PubMed1998

Non-organ specific cancer prevention of ginseng: a prospective study in Korea.

BACKGROUND: A number of studies have reported that increased consumption of natural products reduced the risk of cancer. Our previous case-control studies have shown a significant reduction in the risk of cancer development among those who regularly consumed ginseng. We conducted a prospective cohort study to evaluate the preventive effect of ginseng against cancer on a population residing in a ginseng cultivation area on the basis of the result of case-control studies. METHODS: This study was conducted in Kangwha-eup from August 1987 to December 1992. We studied 4634 people over 40 years old who completed a questionnaire on ginseng intake. In an attempt to obtain detailed information about ginseng intake, we asked them to specify their age at initial intake, their frequency and duration of ginseng intake, the kind of ginseng, etc. Multiple logistic regression was used to estimate relative risks (RR) when controlling simultaneously for covariates. RESULTS: Ginseng consumers had a decreased risk (RR = 0.40, 95% confidence interval [CI] : 0.28-0.56) compared with non-consumers. On the type of ginseng, the RR was 0.31 (95% CI: 0.13-0.74) for fresh ginseng extract consumers and 0.34 (95% CI: 0.20-0.53) for consumers of multiple combinations. There was no cancer death among 24 red ginseng consumers. There was a decreased risk with a rise in the frequency of ginseng intake, showing a dose-response relationship. The RR of ginseng consumers were 0.33 (95% CI: 0.18-0.57) in gastric cancer and 0.30 (95% CI : 0.14-0.65) in lung cancer. Among ginseng preparations, fresh ginseng extract consumers were significantly associated with a decreased risk of gastric cancer (RR = 0.33, 95% CI: 0.12-0.88). CONCLUSIONS: These results strongly suggest that Panax ginseng C.A. Meyer has non-organ specific preventive effect against cancer, providing support for the previous case-control studies.

Adult↗
PubMed1982

Organ-specific autoantibodies in children with common endocrine diseases.

Sera from 438 children were examined for autoantibodies to thyroid microsomes, thyroglobulin, pancreatic islet cells, gastric parietal cells, and adrenocortical cells by indirect hemagglutination and immunofluorescence techniques. A modification of the indirect hemagglutination technique allowed specific detection of low titers of antithyroidal antibodies. The subjects included a control group (117) with no known autoimmune disease, and children with disorders of the thyroid (88), insulin-dependent diabetes mellitus (201), Turner's Syndrome (24), and Addison disease (8). A subject's age at the time of disease onset and the race and sex were correlated with the prevalence of autoantibodies. The coincidence of autoantibodies to components of the thyroid with autoantibodies to gastric parietal cells was increased in children with disorders of the thyroid (94%, 18/19) over that observed in diabetes (29%, 4/14), Turner syndrome (0%), or Addison disease (0%), perhaps indicating different genetic propensities for the development of parietal cell antibodies in these groups. Islet cell antibodies were not found in subjects with Turner syndrome, nor were they more prevalent in white or black subjects with diabetes. The incidence of organ-specific autoantibodies in individuals without overt clinical disease may reflect an altered immunologic state that will lead eventually to autoimmune disease. Islet cell antibodies decline in prevalence in diabetes, whereas thyroid antibodies in disorders of the thyroid do not; this may reflect differences in the pathogenesis of these common autoimmune endocrine disorders in children.

Addison Disease↗
PubMed2001

SJL and NOD macrophages are uniquely characterized by genetically programmed, elevated expression of the IL-12(p40) gene, suggesting a conserved pathway for the induction of organ-specific autoimmunity.

Genetic susceptibility of the SJL mouse to experimental autoimmune encephalomyelitis (EAE) appears, in part, to be a result of genes that promote abnormal development of the pathogenic Type 1 (Th1) phenotype of neuroantigen-specific T-cells. Because antigen-presenting/accessory cells (APCs) produce cytokines that can modulate the development of Th1 and Th2 phenotypes, we addressed whether APCs from SJL mice were genetically programmed for elevated expression of the Th1-promoting cytokine, IL-12. Activated peritoneal macrophages (Mphi; i.e., APC) from naïve SJL mice produced levels of TNF-alpha, IL-1, IL-6, IL-10, and TGF-beta within the range of six normal strains. In contrast, SJL IL-12p40 (in addition to IL-12p70) production was consistently five- to 20-fold greater than that of any normal strain tested, which arose from elevated expression of the IL-12p40 but not the IL-12p35 gene, because p40 mRNA levels were eight- to 15-fold greater than those of normal strains. This aberrancy in IL-12p40 expression appears identical to that observed in the NOD mouse, another strain prone to organ-specific autoimmunity. A genetically programmed bias toward elevated expression of IL-12 in Mphi from the SJL and NOD strains of autoimmunity provides a conserved mechanism for the dominant Th1 development of naive, autoantigen-specific T-cells in these strains. This study is the first demonstration of a genetically programmed aberrant phenotype that is intrinsically expressed within a cell type in the SJL mouse and provides insight into its predisposition for EAE.

Animals↗
PubMed1993

Analysis of regulatory elements involved in stress-induced and organ-specific expression of tobacco acidic and basic beta-1,3-glucanase genes.

Infection of tobacco by tobacco mosaic virus (TMV) induces coordinate expression of genes encoding acidic and basic beta-1,3-glucanase isoforms. These genes are differentially expressed in response to other treatments. Salicylate treatment induces acidic glucanase mRNA to a higher level than basic glucanase mRNA. Ethylene treatment and wounding strongly induce the basic glucanase genes but have little effect on genes encoding the acidic isoforms. Furthermore, the basic glucanase genes are constitutively expressed in roots and lower leaves of healthy plants, whereas the acidic glucanase genes are not. In order to investigate how these expression patterns are established, we fused promoter regions of an acidic and a basic glucanase gene to the beta-glucuronidase (GUS) reporter gene and examined expression of these constructs in transgenic tobacco plants. A fragment of 1750 bp and two 5'-truncated fragments of 650 bp and 300 bp of the acidic glucanase promoter were tested for induction of GUS gene expression after salicylate treatment and TMV infection. Upstream sequences of 1750 bp and 650 bp were sufficient for induction of the reporter gene by salicylate treatment and TMV infection, but the activity of the 300 bp fragment was strongly reduced. The results suggest that the 1750 bp upstream sequence of the acidic glucanase gene contains multiple regulatory elements. For the basic glucanase promoter it is shown that 1476 bp of upstream sequences were able to drive expression in response to TMV infection and ethylene treatment, but no response was found to incision wounding. Furthermore, high GUS activity was found in lower leaves and roots of healthy transgenic plants, carrying the 1476 bp basic glucanase promoter/GUS construct. When the promoter was truncated up to position -446 all activity was lost, indicating that the region between -1476 and -446 of the basic glucanase promoter is necessary for organ-specific and developmentally regulated expression as well as for induced expression in response to infection and other stress treatments.

Base Sequence↗