Aberrant transcription and post-transcriptional processing of hepatitis C virus non-structural genes in transgenic mice.

Abstract:

:Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease worldwide. Since several aspects of the infection remain unresolved, there is a pressing need for a convenient animal model that can mimic the clinical disease and aid the evaluation of treatment strategies. Although some success has been achieved in transgenic approaches for development of rodent models of HCV, transgenic expression of the complete HCV polyprotein or an entire set of the viral non-structural (NS) proteins continues to be a serious challenge. Using northern blot and 5' rapid amplification of cDNA ends (RACE), we unraveled two possible mechanisms that can impede HCV NS transgene expression in the mouse liver. Several truncated transcripts are produced from alternate transcription start sites along the HCV NS sequence within the murine environment, in vivo. Translation of these shorter transcripts is blocked either by the positioning of a contextual stop codon or through a shift in the reading frame. In addition, the complete NS transcript undergoes trans-splicing through 5' recombination with a non-transgene-derived, spliced leader sequence that appends a potential stop codon upstream of the translation start. These findings thus demonstrate that HCV NS-derived transgenes are subject to aberrant transcriptional initiation and post-transcriptional processing in the nucleus of a mouse host. Strategies to prevent such aberrant transcription start/RNA processing might be key to the development of a successful HCV transgenic mouse model.

journal_name

Transgenic Res

journal_title

Transgenic research

authors

Desai MM,Tumurbataar B,Zhang Y,Chan LN,Sun J,Chan TS

doi

10.1007/s11248-011-9494-x

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1273-84

issue

6

eissn

0962-8819

issn

1573-9368

journal_volume

20

pub_type

杂志文章
  • The effect of additional virulence genes on transformation efficiency, transgene integration and expression in rice plants using the pGreen/pSoup dual binary vector system.

    abstract::We assessed the effect of four different virulence (vir) gene combinations on plant transformation efficiency and transgene behaviour in rice using the pGreen/pSoup dual binary vector system. Transformation experiments were conducted using a pGreen vector containing the bar and gusA expression units with, or without, ...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-004-2808-5

    authors: Vain P,Harvey A,Worland B,Ross S,Snape JW,Lonsdale D

    更新日期:2004-12-01 00:00:00

  • Knock-in of diphteria toxin A chain gene at Ins2 locus: effects on islet development and localization of Ins2 expression in the brain.

    abstract::We report here knock-in of diphteria toxin A chain (dta) gene at the Ins2 locus, using the strategy previously employed to insert lacZ under control of the Ins2 promoter. Mutant Ins2(dta/+), Ins2(dta/lacZ) or Ins2(lacZ/+) mouse pups were generated by breeding and analyzed to study the effects of toxigenetic beta-cell ...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-004-9587-x

    authors: Lamotte L,Jackerott M,Bucchini D,Jami J,Joshi RL,Deltour L

    更新日期:2004-10-01 00:00:00

  • Generation of trangenic Xenopus laevis using the Sleeping Beauty transposon system.

    abstract::Using the Sleeping Beauty (SB) transposon system, we have developed a simple method for the generation of Xenopus laevis transgenic lines. The transgenesis protocol is based on the co-injection of the SB transposase mRNA and a GFP-reporter transposon into one-cell stage embryos. Transposase-dependent reporter gene exp...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-006-9014-6

    authors: Sinzelle L,Vallin J,Coen L,Chesneau A,Du Pasquier D,Pollet N,Demeneix B,Mazabraud A

    更新日期:2006-12-01 00:00:00

  • A 7.1 kbp beta-myosin heavy chain promoter, efficient for green fluorescent protein expression, probably induces lethality when overexpressing a mutated transforming growth factor-beta type II receptor in transgenic mice.

    abstract::The roles of transforming growth factor-beta (TGFbeta) in heart or skeletal muscle development and physiology are still the subject of controversies. Our aim was to block, in transgenic mice, the TGFbeta signalling pathway by a dominant negative mutant of the TGFbeta type II receptor fused to the enhanced green fluore...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-004-5788-6

    authors: Allegra S,Bouazza L,Benetollo C,Li JY,Langlois D

    更新日期:2005-02-01 00:00:00

  • Skeletal defects in Osterix-Cre transgenic mice.

    abstract::Cre/loxP recombination is a powerful strategy widely used for in vivo conditional gene targeting. This technique has made possible many important discoveries of gene function in normal and disease biology. However, due to the transgenic nature of most Cre mouse strains undesired phenotypes occasionally occur in Cre mi...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-014-9828-6

    authors: Huang W,Olsen BR

    更新日期:2015-02-01 00:00:00

  • Uniform GFP-expression in transgenic medaka (Oryzias latipes) at the F0 generation.

    abstract::A green fluorescent protein (GFP) cDNA flanked by inverted terminal repeats (ITR) of adeno-associated virus was constructed. The construct sharply improved the efficiency and specificity of the transient expression of genes driven by two general promoters (cytomegalovirus and medaka beta-actin) and one muscle-specific...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1023/a:1016671513425

    authors: Chou CY,Horng LS,Tsai HJ

    更新日期:2001-08-01 00:00:00

  • Production of biologically active human granulocyte colony stimulating factor in the milk of transgenic goat.

    abstract::We have developed a transgenic female goat harboring goat beta-casein promoter/human granulocyte colony stimulating factor (G-CSF) fusion gene by microinjection into fertilized one-cell goat zygotes. Human G-CSF was produced at levels of up to 50 microg/ml in transgenic goat milk. Its biological activity was equivalen...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1023/a:1008972010351

    authors: Ko JH,Lee CS,Kim KH,Pang MG,Koo JS,Fang N,Koo DB,Oh KB,Youn WS,Zheng GD,Park JS,Kim SJ,Han YM,Choi IY,Lim J,Shin ST,Jin SW,Lee KK,Yoo OJ

    更新日期:2000-06-01 00:00:00

  • Opportunities for manipulating the seed protein composition of wheat and barley in order to improve quality.

    abstract::Wheat and barley are the major temperate cereals, being used for food, feed and industrial raw material. However, in all cases the quality may be limited by the amount, composition and properties of the grain storage proteins. We describe how a combination of biochemical and molecular studies has led to an understandi...

    journal_title:Transgenic research

    pub_type: 杂志文章,评审

    doi:10.1007/BF01976021

    authors: Shewry PR,Tatham AS,Halford NG,Barker JH,Hannappel U,Gallois P,Thomas M,Kreis M

    更新日期:1994-01-01 00:00:00

  • Uniform accumulation of recombinant miraculin protein in transgenic tomato fruit using a fruit-ripening-specific E8 promoter.

    abstract::The E8 promoter, a tomato fruit-ripening-specific promoter, and the CaMV 35S promoter, a constitutive promoter, were used to express the miraculin gene encoding the taste-modifying protein in tomato. The accumulation of miraculin protein and mRNA was compared among transgenic tomatoes expressing the miraculin gene dri...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-011-9495-9

    authors: Hirai T,Kim YW,Kato K,Hiwasa-Tanase K,Ezura H

    更新日期:2011-12-01 00:00:00

  • Conditional gene expression in the respiratory epithelium of the mouse.

    abstract::Transgenic mouse models mediating conditional temporal and spatial regulation of gene expression to the respiratory epithelium were developed utilizing the reverse tetracycline transactivator (rtTA) expressed under the control of SP-C and CCSP promoters. Luciferase activity was detected in the lungs of fetal and adult...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1023/a:1013986627504

    authors: Perl AK,Tichelaar JW,Whitsett JA

    更新日期:2002-02-01 00:00:00

  • Expression of the isopentenyl transferase gene is regulated by auxin in transgenic tobacco tissues.

    abstract::The isopentenyl transferase gene (ipt) from Agrobacterium tumefaciens was isolated and introduced, via a disarmed binary vector, into tobacco using the Agrobacterium tumefaciens-mediated gene transfer system. The expression of the ipt gene was monitored by RNA hybridization, western blotting and cytokinin analysis. Th...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/BF01979922

    authors: Zhang XD,Letham DS,Zhang R,Higgins TJ

    更新日期:1996-01-01 00:00:00

  • Matrix attachment regions increase the efficiency and stability of RNA-mediated resistance to tomato spotted wilt virus in transgenic tobacco.

    abstract::Matrix attachment regions (MARs) are DNA elements that can increase and stabilize transgene expression. We investigated the effect of the RB7 MAR on transgenic virus resistance. Constructs for resistance to tomato spotted wilt virus (TSWV) with and without flanking RB7 MARs were used to transform tobacco and produce h...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-004-5413-8

    authors: Levin JS,Thompson WF,Csinos AS,Stephenson MG,Weissinger AK

    更新日期:2005-04-01 00:00:00

  • Phytohormones and rice crop yield: strategies and opportunities for genetic improvement.

    abstract::To feed an estimated world population of 8.9 billion by 2050, strategies for increasing grain production must be developed. Several agronomically important traits for increasing yield, such as plant height, grain number, and leaf erectness, have recently been characterized in rice (Oryza sativa L.). These traits are r...

    journal_title:Transgenic research

    pub_type: 杂志文章,评审

    doi:10.1007/s11248-006-0024-1

    authors: Sakamoto T

    更新日期:2006-08-01 00:00:00

  • An SAR sequence containing 395 bp DNA fragment mediates enhanced, gene-dosage-correlated expression of a chimaeric heat shock gene in transgenic tobacco plants.

    abstract::A 395 bp fragment located downstream from the soybean heat shock gene Gmhsp 17.6-L exhibits several characteristics of scaffold attachment region (SAR) sequences. It contains matrix consensus elements, a topoisomerase II binding sequence and it associates with the isolated nuclear scaffold of soybean in vitro. Chimaer...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/BF01969382

    authors: Schöffl F,Schröder G,Kliem M,Rieping M

    更新日期:1993-03-01 00:00:00

  • Ubiquitin promoter-based vectors for high-level expression of selectable and/or screenable marker genes in monocotyledonous plants.

    abstract::A set of plasmids has been constructed utilizing the promoter, 5' untranslated exon, and first intron of the maize ubiquitin (Ubi-1) gene to drive expression of protein coding sequences of choice. Plasmids containing chimaeric genes for ubiquitin-luciferase (Ubi-Luc), ubiquitin-beta-glucuronidase (Ubi-GUS), and ubiqui...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/BF01969712

    authors: Christensen AH,Quail PH

    更新日期:1996-05-01 00:00:00

  • Male-biased fasting-induced changes in hepatic tauro-cholic acid and plasma cholesterol in Sult2a8-haplodeficient mice.

    abstract::SULT2A8 is a male-predominant and liver-specific mouse cytosolic sulfotransferase (SULT) that sulfonates 7α-hydroxyl (7α-OH) bile acids in vitro. Sulfonation regulates bile acid homeostasis, which in turn regulates cholesterol and energy metabolism. Using the Sult2a8-heterozygous (HT) mouse model created earlier in ou...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-020-00215-w

    authors: Wang K,Chan MY,Xu J,Li PS,Liu X,Lee AY,Lee SS,Cheung WT

    更新日期:2020-12-01 00:00:00

  • Bovine alpha s1-casein gene sequences direct high level expression of human granulocyte-macrophage colony-stimulating factor in the milk of transgenic mice.

    abstract::The generation is reported of transgenic mice expressing human granulocyte-macrophage colony-stimulating factor (GM-CSF) or human erythropoietin (EPO) under the control of bovine alpha s1-casein regulatory sequences. GM-CSF expression was specific to the mammary gland, and levels of human GM-CSF in transgenic mouse mi...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1023/a:1018461201385

    authors: Uusi-Oukari M,Hyttinen JM,Korhonen VP,Västi A,Alhonen L,Jänne OA,Jänne J

    更新日期:1997-01-01 00:00:00

  • Agroinfiltration as a tool for transient expression of cre recombinase in vivo.

    abstract::Agroinfiltration was used to express transiently cre recombinase from bacteriophage P1 in planta. Activation of gfp expression after cre-mediated excision of a bar intervening sequence served as a marker to monitor site-specific recombination events in lox-target N. benthamiana plants. Gfp expressing regenerants from ...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-005-8293-7

    authors: Kopertekh L,Schiemann J

    更新日期:2005-10-01 00:00:00

  • Proposed criteria for identifying GE crop plants that pose a low or negligible risk to the environment under conditions of low-level presence in seed.

    abstract::The low-level presence (LLP) of genetically engineered (GE) seeds that have been approved in the country of origin but not the country of import presents challenges for regulators in both seed importing and exporting countries, as well as for the international seed trade and the farmers who rely on it. In addition to ...

    journal_title:Transgenic research

    pub_type: 杂志文章,评审

    doi:10.1007/s11248-015-9899-z

    authors: Roberts A,Finardi-Filho F,Hegde S,Kiekebusch J,Klimpel G,Krieger M,Lema MA,Macdonald P,Nari C,Rubinstein C,Slutsky B,Vicien C

    更新日期:2015-10-01 00:00:00

  • High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I.

    abstract::To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/BF02528779

    authors: Swanson ME,Hughes TE,Denny IS,France DS,Paterniti JR Jr,Tapparelli C,Gfeller P,Bürki K

    更新日期:1992-05-01 00:00:00

  • In vivo characterization of plant promoter element interaction using synthetic promoters.

    abstract::Short directly-repeated (DR) DNA enhancer elements of plant viral origin were analyzed for their ability, both individually and in combination, to influence in vivo transcription when inserted upstream from a minimal CaMV35S promoter. Synthetic promoters containing multiple copies and/or combinations of DR cassettes w...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-007-9117-8

    authors: Cazzonelli CI,Velten J

    更新日期:2008-06-01 00:00:00

  • Identification of transgenic mice by direct PCR analysis of lysates of epithelial cells obtained from the inner surface of the rectum.

    abstract::Conventional screening protocols for transgene integration in mice employ tail tips or blood samples as sources to obtain genomic DNA preparations. We have developed a simple alternative non-surgical method. Epithelial cells are scraped off the inner surface of the rectum with a sterile plastic inoculation loop and ar...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1023/a:1008824509988

    authors: Lahm H,Hoeflich A,Rieger N,Wanke R,Wolf E

    更新日期:1998-03-01 00:00:00

  • Regulation of human protein C gene expression by the mouse WAP promoter.

    abstract::A 4.1 kb mouse whey acidic protein (mWAP) promoter was cloned from a C57BL/6 cosmid library. The tissue-specific and developmental pattern of expression of a hybrid gene comprised of the mWAP promoter fragment and the human protein C (HPC) gene was analysed in transgenic mice. The corresponding RNA was detected mainly...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/BF01976765

    authors: Paleyanda RK,Zhang DW,Hennighausen L,McKnight RA,Lubon H

    更新日期:1994-11-01 00:00:00

  • Cis effect of lacZ sequences in transgenic mice.

    abstract::Transgenic mice carrying the 3-hydroxy-3-methylglutarylCoA reductase (HMG) promoter driving the Escherichia coli beta-galactosidase (lacZ) gene did not display the expected ubiquitous and constitutive expression in HMG-lacZ transgenic mice. The same promoter is however able to drive ubiquitous expression of the chlora...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/BF01976173

    authors: Paldi A,Deltour L,Jami J

    更新日期:1993-11-01 00:00:00

  • Insights into the regulatory characteristics of silkworm fibroin gene promoters using a modified Gal4/UAS system.

    abstract::The silkworm Bombyx mori is a valuable insect that synthesizes bulk amounts of fibroin protein in its posterior silk gland (PSG) and weaves these proteins into silk cocoons. The mechanism by which the fibroin protein is efficiently synthesized and precisely regulated is an important aspect that has yet to be fully elu...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-019-00175-w

    authors: Liu R,Zeng W,Tan T,Chen T,Luo Q,Qu D,Tang Y,Long D,Xu H

    更新日期:2019-12-01 00:00:00

  • Comparison of male chimeric mice generated from microinjection of JM8.N4 embryonic stem cells into C57BL/6J and C57BL/6NTac blastocysts.

    abstract::To identify ways to improve the efficiency of generating chimeric mice via microinjection of blastocysts with ES cells, we compared production and performance of ES-cell derived chimeric mice using blastocysts from two closely related and commonly used sub-strains of C57BL/6. Chimeras were produced by injection of the...

    journal_title:Transgenic research

    pub_type: 信件

    doi:10.1007/s11248-012-9605-3

    authors: Fielder TJ,Yi CS,Masumi J,Waymire KG,Chen HW,Wang S,Shi KX,Wallace DC,MacGregor GR

    更新日期:2012-12-01 00:00:00

  • Over-expression of OSRIP18 increases drought and salt tolerance in transgenic rice plants.

    abstract::Both drought and high salinity stresses are major abiotic factors that limit the yield of agricultural crops. Transgenic techniques have been regarded as effective ways to improve crops in their tolerance to these abiotic stresses. Functional characterization of genes is the prerequisite to identify candidates for suc...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-011-9568-9

    authors: Jiang SY,Bhalla R,Ramamoorthy R,Luan HF,Venkatesh PN,Cai M,Ramachandran S

    更新日期:2012-08-01 00:00:00

  • Effect of volunteers on maize gene flow.

    abstract::Regulatory approvals for deliberate release of GM maize events into the environment have lead to real situations of coexistence between GM and non-GM, with some fields being cultivated with GM and conventional varieties in successive seasons. Given the common presence of volunteer plants in maize fields in temperate a...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-009-9250-7

    authors: Palaudelmàs M,Peñas G,Melé E,Serra J,Salvia J,Pla M,Nadal A,Messeguer J

    更新日期:2009-08-01 00:00:00

  • Improved soybean transformation for efficient and high throughput transgenic production.

    abstract::Although genetic transformation of soybean dates back to over two decades, the process remains inefficient. Here, we report the development of an organogenesis-based transformation method of soybean that resulted in an average transformation frequency of 18.7%. This improved method resorts to Agrobacterium-mediated tr...

    journal_title:Transgenic research

    pub_type: 杂志文章

    doi:10.1007/s11248-020-00198-8

    authors: Pareddy D,Chennareddy S,Anthony G,Sardesai N,Mall T,Minnicks T,Karpova O,Clark L,Griffin D,Bishop B,Shumway N,Samuel P,Smith K,Sarria R

    更新日期:2020-06-01 00:00:00

  • A study on the influence of different promoter and 5'UTR (URM) cassettes from Arabidopsis thaliana on the expression level of the reporter gene β glucuronidase in tobacco and cotton.

    abstract::Several reports of promoters from plants, viral and artificial origin that confer high constitutive expression are known. Among these the CaMV 35S promoter is used extensively for transgene expression in plants. We identified candidate promoters from Arabidopsis based on their transcript levels (meta-analysis of avail...

    journal_title:Transgenic research

    pub_type: 杂志文章,meta分析

    doi:10.1007/s11248-013-9757-9

    authors: Agarwal P,Garg V,Gautam T,Pillai B,Kanoria S,Burma PK

    更新日期:2014-04-01 00:00:00