Controlled insertional mutagenesis using a LINE-1 (ORFeus) gene-trap mouse model.

Abstract:

:A codon-optimized mouse LINE-1 element, ORFeus, exhibits dramatically higher retrotransposition frequencies compared with its native long interspersed element 1 counterpart. To establish a retrotransposon-mediated mouse model with regulatable and potent mutagenic capabilities, we generated a tetracycline (tet)-regulated ORFeus element harboring a gene-trap cassette. Here, we show that mice expressing tet-ORFeus broadly exhibit robust retrotransposition in somatic tissues when treated with doxycycline. Consistent with a significant mutagenic burden, we observed a reduced number of double transgenic animals when treated with high-level doxycycline during embryogenesis. Transgene induction in skin resulted in a white spotting phenotype due to somatic ORFeus-mediated mutations that likely disrupt melanocyte development. The data suggest a high level of transposition in melanocyte precursors and consequent mutation of genes important for melanoblast proliferation, differentiation, or migration. These findings reveal the utility of a retrotransposon-based mutagenesis system as an alternative to existing DNA transposon systems. Moreover, breeding these mice to different tet-transactivator/reversible tet-transactivator lines supports broad functionality of tet-ORFeus because of the potential for dose-dependent, tissue-specific, and temporal-specific mutagenesis.

authors

O'Donnell KA,An W,Schrum CT,Wheelan SJ,Boeke JD

doi

10.1073/pnas.1302504110

subject

Has Abstract

pub_date

2013-07-16 00:00:00

pages

E2706-13

issue

29

eissn

0027-8424

issn

1091-6490

pii

1302504110

journal_volume

110

pub_type

杂志文章
  • Ribosome recycling step in yeast cytoplasmic protein synthesis is catalyzed by eEF3 and ATP.

    abstract::After each round of protein biosynthesis, the posttermination complex (PoTC) consisting of a ribosome, mRNA, and tRNA must be disassembled into its components for a new round of translation. Here, we show that a Saccharomyces cerevisiae model PoTC was disassembled by ATP and eukaryotic elongation factor 3 (eEF3). GTP ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1006247107

    authors: Kurata S,Nielsen KH,Mitchell SF,Lorsch JR,Kaji A,Kaji H

    更新日期:2010-06-15 00:00:00

  • Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin.

    abstract::Dynamic signals linking the actin cytoskeleton and cell adhesion receptors are essential for morphogenesis during development and normal tissue homeostasis. Abi1 is a central regulator of actin polymerization through interactions with multiple protein complexes. However, the in vivo role of Abi1 remains to be defined....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1012316108

    authors: Ring C,Ginsberg MH,Haling J,Pendergast AM

    更新日期:2011-01-04 00:00:00

  • Recombinant thyroid hormone receptor and retinoid X receptor stimulate ligand-dependent transcription in vitro.

    abstract::The thyroid hormone and retinoid X receptors form a heterodimer with each other and mediate thyroid hormone (T3)-dependent transcription. Retinoid X receptor, in addition, forms a homodimer and mediates 9-cis-retinoic acid-dependent transcription. Here, recombinant thyroid hormone receptor and recombinant retinoid X r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.5.1647

    authors: Lee IJ,Driggers PH,Medin JA,Nikodem VM,Ozato K

    更新日期:1994-03-01 00:00:00

  • Structural studies of the scrapie prion protein by electron crystallography.

    abstract::Because the insolubility of the scrapie prion protein (PrP(Sc)) has frustrated structural studies by x-ray crystallography or NMR spectroscopy, we used electron crystallography to characterize the structure of two infectious variants of the prion protein. Isomorphous two-dimensional crystals of the N-terminally trunca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.052703499

    authors: Wille H,Michelitsch MD,Guenebaut V,Supattapone S,Serban A,Cohen FE,Agard DA,Prusiner SB

    更新日期:2002-03-19 00:00:00

  • A new ultrafast energy funneling material harvests three times more diffusive solar energy for GaInP photovoltaics.

    abstract::There is no theoretical limit in using molecular networks to harvest diffusive sun photons on large areas and funnel them onto much smaller areas of highly efficient but also precious energy-converting materials. The most effective concept reported so far is based on a pool of randomly oriented, light-harvesting donor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2019198117

    authors: Willich MM,Wegener L,Vornweg J,Hohgardt M,Nowak J,Wolter M,Jacob CR,Walla PJ

    更新日期:2020-12-29 00:00:00

  • Physical association of CD4 and the T-cell receptor can be induced by anti-T-cell receptor antibodies.

    abstract::CD4 can physically associate with the CD3-T-cell receptor complex as visualized in cocapping experiments. This association occurs when the T-cell receptor is cross-linked by certain anti-variable region antibodies that appear to induce a conformational change in the receptor such that it associate with CD4. Similar as...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.9.3311

    authors: Rojo JM,Saizawa K,Janeway CA Jr

    更新日期:1989-05-01 00:00:00

  • Isolation of a glycogen synthase I kinase that is independent of adenosine 3':5'-monophosphate.

    abstract::Three protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) were detected when the soluble fraction of rabbit kidney medulla was chromatographed on DEAE-cellulose with a linear NaC1 gradient. The first two kinases eluted (Peak 1 and Peak II) were cyclic-AMP-dependent, wheras Peak III was cyclic-AMP-independent...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.6.2197

    authors: Schlender KK,Reimann EM

    更新日期:1975-06-01 00:00:00

  • Structural transitions within human Rad51 nucleoprotein filaments.

    abstract::Rad51 is a core component of the eukaryotic homologous recombination machinery and is responsible for key mechanistic steps during strand invasion. Higher order oligomers of Rad51 display a remarkable degree of structural variation, forming rings, compressed filaments, and elongated filaments. It is unclear whether Ra...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0811465106

    authors: Robertson RB,Moses DN,Kwon Y,Chan P,Chi P,Klein H,Sung P,Greene EC

    更新日期:2009-08-04 00:00:00

  • Conformation of acetylcholine bound to the nicotinic acetylcholine receptor.

    abstract::We report here the biologically active conformation of acetylcholine when bound to the high-affinity state of the receptor from Torpedo californica. The acetylcholine conformation was determined in the free and bound states by proton NMR two-dimensional nuclear Overhauser effects. In agreement with x-ray crystallograp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.18.6721

    authors: Behling RW,Yamane T,Navon G,Jelinski LW

    更新日期:1988-09-01 00:00:00

  • Synergistic fibrinolysis: combined effects of plasminogen activators and an antibody that inhibits alpha 2-antiplasmin.

    abstract::To improve the efficacy of plasminogen activators, we produced a monoclonal antibody (RWR) that inhibits human alpha 2-antiplasmin (alpha 2AP). In addition to inhibiting alpha 2AP in plasma, RWR binds to and inhibits fibrin cross-linked alpha 2AP and reproduces the "spontaneous" clot lysis that is the hallmark of huma...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.3.1114

    authors: Reed GL 3rd,Matsueda GR,Haber E

    更新日期:1990-02-01 00:00:00

  • F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase.

    abstract::There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1608304113

    authors: Oliver JD,Sibley GEM,Beckmann N,Dobb KS,Slater MJ,McEntee L,du Pré S,Livermore J,Bromley MJ,Wiederhold NP,Hope WW,Kennedy AJ,Law D,Birch M

    更新日期:2016-11-08 00:00:00

  • Behavioral experiments on biased voting in networks.

    abstract::Many distributed collective decision-making processes must balance diverse individual preferences with a desire for collective unity. We report here on an extensive session of behavioral experiments on biased voting in networks of individuals. In each of 81 experiments, 36 human subjects arranged in a virtual network ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0808147106

    authors: Kearns M,Judd S,Tan J,Wortman J

    更新日期:2009-02-03 00:00:00

  • poc1: an Arabidopsis mutant perturbed in phytochrome signaling because of a T DNA insertion in the promoter of PIF3, a gene encoding a phytochrome-interacting bHLH protein.

    abstract::The phytochrome family of informational photoreceptors has a central role in regulating light-responsive gene expression, but the mechanism of intracellular signal transduction has remained elusive. In a genetic screen for T DNA-tagged Arabidopsis mutants affected in early signaling intermediates, we identified poc1 (...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.10.5832

    authors: Halliday KJ,Hudson M,Ni M,Qin M,Quail PH

    更新日期:1999-05-11 00:00:00

  • Genomic DNA fingerprinting by restriction fragment end labeling.

    abstract::A typing method for bacteria was developed and applied to several species, including Escherichia coli and Actinobacillus actinomycetemcomitans. Total genomic DNA was digested with a restriction endonuclease, and fragments were enabled with [alpha-32P]dATP by using the Klenow fragment of DNA polymerase and separated by...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.12.5572

    authors: van Steenbergen TJ,Colloms SD,Hermans PW,de Graaff J,Plasterk RH

    更新日期:1995-06-06 00:00:00

  • COST1 regulates autophagy to control plant drought tolerance.

    abstract::Plants balance their competing requirements for growth and stress tolerance via a sophisticated regulatory circuitry that controls responses to the external environments. We have identified a plant-specific gene, COST1 (constitutively stressed 1), that is required for normal plant growth but negatively regulates droug...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1918539117

    authors: Bao Y,Song WM,Wang P,Yu X,Li B,Jiang C,Shiu SH,Zhang H,Bassham DC

    更新日期:2020-03-31 00:00:00

  • Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid.

    abstract::Human T cell leukemia virus type 1 (HTLV-1) has evolved a remarkable strategy to thwart the antiviral effects of the cellular cytidine deaminase APOBEC3G (hA3G). HTLV-1 infects T lymphocytes in vivo, where, like HIV-1, it is likely to encounter hA3G. HIV-1 counteracts the innate antiviral activity of hA3G by producing...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0609444104

    authors: Derse D,Hill SA,Princler G,Lloyd P,Heidecker G

    更新日期:2007-02-20 00:00:00

  • IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection.

    abstract::Mounting effective T cell responses is critical for eliciting long-lasting immunity following viral infection and vaccination. A multitude of inhibitory and stimulatory factors are induced following infection, and it is the compilation of these signals that quantitatively and qualitatively program the ensuing effector...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914500107

    authors: Brooks DG,Walsh KB,Elsaesser H,Oldstone MB

    更新日期:2010-02-16 00:00:00

  • New thioredoxin targets in the unicellular photosynthetic eukaryote Chlamydomonas reinhardtii.

    abstract::Proteomics were used to identify the proteins from the eukaryotic unicellular green alga Chlamydomonas reinhardtii that can be reduced by thioredoxin. These proteins were retained specifically on a thioredoxin affinity column made of a monocysteinic thioredoxin mutant able to form mixed disulfides with its targets. Of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0402221101

    authors: Lemaire SD,Guillon B,Le Maréchal P,Keryer E,Miginiac-Maslow M,Decottignies P

    更新日期:2004-05-11 00:00:00

  • Structure and regulation of the rat 1,25-dihydroxyvitamin D3 receptor.

    abstract::Complementary DNA clones encoding the entire rat 1,25-dihydroxyvitamin D3 receptor were isolated, and the total 423-amino acid sequence was deduced. The amino acid sequence of the rat receptor is similar but not identical to the reported human receptor sequence. The cysteine-rich DNA-binding domain is completely conse...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.24.9499

    authors: Burmester JK,Wiese RJ,Maeda N,DeLuca HF

    更新日期:1988-12-01 00:00:00

  • A strategy for the identification of proteins targeted by thioredoxin.

    abstract::Thioredoxins are 12-kDa proteins functional in the regulation of cellular processes throughout the animal, plant, and microbial kingdoms. Growing evidence with seeds suggests that an h-type of thioredoxin, reduced by NADPH via NADP-thioredoxin reductase, reduces disulfide bonds of target proteins and thereby acts as a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.071041998

    authors: Yano H,Wong JH,Lee YM,Cho MJ,Buchanan BB

    更新日期:2001-04-10 00:00:00

  • Female gamete competition in an ancient angiosperm lineage.

    abstract::In Trimenia moorei, an extant member of the ancient angiosperm clade Austrobaileyales, we found a remarkable pattern of female gametophyte (egg-producing structure) development that strikingly resembles that of pollen tubes and their intrasexual competition within the maternal pollen tube transmitting tissues of most ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1104697108

    authors: Bachelier JB,Friedman WE

    更新日期:2011-07-26 00:00:00

  • Timescale-dependent shaping of correlation by olfactory bulb lateral inhibition.

    abstract::Neurons respond to sensory stimuli by altering the rate and temporal pattern of action potentials. These spike trains both encode and propagate information that guides behavior. Local inhibitory networks can affect the information encoded and propagated by neurons by altering correlations between different spike train...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1015165108

    authors: Giridhar S,Doiron B,Urban NN

    更新日期:2011-04-05 00:00:00

  • Neural basis of contagious itch and why some people are more prone to it.

    abstract::Watching someone scratch himself can induce feelings of itchiness in the perceiver. This provides a unique opportunity to characterize the neural basis of subjective experiences of itch, independent of changes in peripheral inputs. In this study, we first established that the social contagion of itch is essentially a ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1216160109

    authors: Holle H,Warne K,Seth AK,Critchley HD,Ward J

    更新日期:2012-11-27 00:00:00

  • Genomic imprinting effects on adult body composition in mice.

    abstract::Genomic imprinting results in the differential expression of genes, depending on which allele is inherited from the mother and which from the father. The effects of such differential gene expression are reflected in phenotypic differences between the reciprocal heterozygotes (Aa vs. aA). Although many imprinted genes ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0706562105

    authors: Cheverud JM,Hager R,Roseman C,Fawcett G,Wang B,Wolf JB

    更新日期:2008-03-18 00:00:00

  • Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2',3'-dideoxynucleoside activities against replication of human immunodeficiency virus.

    abstract::We and other groups have recently reported the potentiation by ribonucleotide reductase inhibitors such as hydroxyurea of the anti-human immunodeficiency virus type 1 (HIV-1) activity of purine and pyrimidine 2',3'-dideoxynucleosides in both resting and phytohemagglutinin-stimulated peripheral blood mononuclear cells....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.18.8333

    authors: Gao WY,Johns DG,Chokekuchai S,Mitsuya H

    更新日期:1995-08-29 00:00:00

  • Nanoscale morphological evolution of monocrystalline Pt surfaces during cathodic corrosion.

    abstract::This paper studies the cathodic corrosion of a spherical single crystal of platinum in an aqueous alkaline electrolyte, to map out the detailed facet dependence of the corrosion structures forming during this still largely unexplored electrochemical phenomenon. We find that anisotropic corrosion of the platinum electr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2017086117

    authors: Arulmozhi N,Hersbach TJP,Koper MTM

    更新日期:2020-12-22 00:00:00

  • Integration of Agrobacterium tumefaciens T-DNA in the Saccharomyces cerevisiae genome by illegitimate recombination.

    abstract::Agrobacterium tumefaciens can transfer part of its Ti plasmid, the T-DNA, to plant cells where it integrates into the nuclear genome via illegitimate recombination. Integration of the T-DNA results in small deletions of the plant target DNA, and may lead to truncation of the T-DNA borders and the production of filler ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.26.15272

    authors: Bundock P,Hooykaas PJ

    更新日期:1996-12-24 00:00:00

  • Point-of-care device to diagnose and monitor neonatal jaundice in low-resource settings.

    abstract::Newborns are at increased risk of jaundice, a condition in which excess bilirubin accumulates in blood. Left untreated, jaundice can lead to neurological impairment and death. Jaundice resulting from unconjugated hyperbilirubinemia is easily treated with exposure to blue light, and phototherapy systems have been devel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1714020114

    authors: Keahey PA,Simeral ML,Schroder KJ,Bond MM,Mtenthaonnga PJ,Miros RH,Dube Q,Richards-Kortum RR

    更新日期:2017-12-19 00:00:00

  • Cdc20 associates with the kinase aurora2/Aik.

    abstract::Cdc20/fizzy family proteins are involved in activation of the anaphase-promoting complex/cyclosome, which catalyzes the ubiquitin-dependent proteolysis of cell cycle regulatory proteins such as anaphase inhibitors and mitotic cyclins, leading to chromosome segregation and exit from mitosis. Previous work has shown tha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.13.7306

    authors: Farruggio DC,Townsley FM,Ruderman JV

    更新日期:1999-06-22 00:00:00

  • Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain.

    abstract::The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using [3H]batrachotoxinin-A 20-alpha-benzoate (BT...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.9.3051

    authors: Worley PF,Baraban JM

    更新日期:1987-05-01 00:00:00