Simultaneous gene editing by injection of mRNAs encoding transcription activator-like effector nucleases into mouse zygotes.

Abstract:

:Injection of transcription activator-like effector nucleases (TALEN) mRNAs into mouse zygotes transferred into foster mothers efficiently generated founder mice with heritable mutations in targeted genes. Immunofluorescence visualization of phosphorylated histone 2A (γH2AX) combined with fluorescence in situ hybridization revealed that TALEN pairs targeting the Agouti locus induced site-directed DNA breaks in zygotes within 6 h of injection, an activity that continued at reduced efficiency in two-cell embryos. TALEN-Agouti mRNAs injected into zygotes of brown FvB × C57BL/6 hybrid mice generated completely black pups, confirming that mutations were induced prior to, and/or early after, cell division. Founder mice, many of which were mosaic, transmitted altered Agouti alleles to F1 pups to yield an allelic series of mutant strains. Although mutations were targeted to "spacer" sequences flanked by TALEN binding sites, larger deletions that extended beyond the TALEN-binding sequences were also detected and were similarly inherited through the germ line. Zygotic coinjection of TALEN mRNAs directed to the Agouti, miR-205, and the Arf tumor suppressor loci yielded pups containing frequent and heritable mutations of two or three genes. Simultaneous gene editing in zygotes affords an efficient approach for producing mice with compound mutant phenotypes, bypassing constraints of conventional mouse knockout technology in embryonic stem cells.

journal_name

Mol Cell Biol

authors

Li C,Qi R,Singleterry R,Hyle J,Balch A,Li X,Sublett J,Berns H,Valentine M,Valentine V,Sherr CJ

doi

10.1128/MCB.00023-14

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

1649-58

issue

9

eissn

0270-7306

issn

1098-5549

pii

MCB.00023-14

journal_volume

34

pub_type

杂志文章
  • Evidence suggesting that the ARS elements associated with silencers of the yeast mating-type locus HML do not function as chromosomal DNA replication origins.

    abstract::The silent mating-type loci of Saccharomyces cerevisiae, HML and HMR, are flanked by transcriptional silencers that have ARS activity (i.e., they function as replication origins when in plasmids). To test whether these ARS elements are chromosomal origins, we mapped origins near HML (close to the left telomere of chro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.10.5346

    authors: Dubey DD,Davis LR,Greenfeder SA,Ong LY,Zhu JG,Broach JR,Newlon CS,Huberman JA

    更新日期:1991-10-01 00:00:00

  • Linear distance from the locus control region determines epsilon-globin transcriptional activity.

    abstract::Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00602-07

    authors: Shimotsuma M,Matsuzaki H,Tanabe O,Campbell AD,Engel JD,Fukamizu A,Tanimoto K

    更新日期:2007-08-01 00:00:00

  • Telomerase is processive.

    abstract::Telomerase synthesizes tandem repeats of the sequence d(TTGGGG) onto input d(TTGGGG)n primer oligonucleotides (C. W. Greider and E. H. Blackburn, Cell 43:405-413). An intrinsic RNA component of the enzyme provides the template for d(TTGGGG)n repeat synthesis [C. W. Greider and E. H. Blackburn, Nature (London) 337:331-...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.9.4572

    authors: Greider CW

    更新日期:1991-09-01 00:00:00

  • Tissue-specific distribution of a novel C-terminal truncation retinoic acid receptor mutant which acts as a negative repressor in a promoter- and cell-type-specific manner.

    abstract::A cDNA clone which encodes a truncation form of the gamma subtype of the retinoic acid receptor (RAR gamma) has been isolated. The mutant RAR gamma (RAR gamma Bm382) has lost its 65 C-terminal amino acids, thus truncating a part of the dimerization and activation domains. By using a reverse transcription-coupled PCR t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.4.1961

    authors: Matsui T,Sashihara S

    更新日期:1995-04-01 00:00:00

  • Multiple distinct splicing enhancers in the protein-coding sequences of a constitutively spliced pre-mRNA.

    abstract::We have identified multiple distinct splicing enhancer elements within protein-coding sequences of the constitutively spliced human beta-globin pre-mRNA. Each of these highly conserved sequences is sufficient to activate the splicing of a heterologous enhancer-dependent pre-mRNA. One of these enhancers is activated by...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.261

    authors: Schaal TD,Maniatis T

    更新日期:1999-01-01 00:00:00

  • Cooperative action of multiple cis-acting elements is required for N-myc expression in branchial arches: specific contribution of GATA3.

    abstract::The precise expression of the N-myc proto-oncogene is essential for normal mammalian development, whereas altered N-myc gene regulation is known to be a determinant factor in tumor formation. Using transgenic mouse embryos, we show that N-myc sequences from kb -8.7 to kb +7.2 are sufficient to reproduce the N-myc embr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00353-09

    authors: Potvin E,Beuret L,Cadrin-Girard JF,Carter M,Roy S,Tremblay M,Charron J

    更新日期:2010-11-01 00:00:00

  • Substitutions in the hydrophobic core of the alpha-factor receptor of Saccharomyces cerevisiae permit response to Saccharomyces kluyveri alpha-factor and to antagonist.

    abstract::Mutations in the Saccharomyces cerevisiae alpha-factor receptor that lead to improved response to Saccharomyces kluyveri alpha-factor were identified and sequenced. Mutants were isolated from cells bearing randomly mutagenized receptor gene (STE2) plasmids by an in vivo screen. Five mutations lead to substitutions in ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.9.3959

    authors: Marsh L

    更新日期:1992-09-01 00:00:00

  • Differential regulation of E2F1, DP1, and the E2F1/DP1 complex by ARF.

    abstract::The tumor suppressor protein ARF inhibits MDM2 to activate and stabilize p53. Recent studies provided evidence for p53-independent tumor suppression functions of ARF. For example, it has been shown that ARF induces proteolysis of certain E2F species, including E2F1. In addition, ARF relocalizes E2F1 from the nucleopla...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.24.8398-8408.2002

    authors: Datta A,Nag A,Raychaudhuri P

    更新日期:2002-12-01 00:00:00

  • Studies of partially transforming polyomavirus mutants establish a role for phosphatidylinositol 3-kinase in activation of pp70 S6 kinase.

    abstract::Infection of mouse fibroblasts by wild-type polyomavirus results in increased phosphorylation of ribosomal protein S6 (D.A. Talmage, J. Blenis, and T.L. Benjamin, Mol. Cell. Biol. 8:2309-2315, 1988). Here we identify pp70 S6 kinase (pp70S6K) as a target for signal transduction events leading from polyomavirus middle t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.6.2728

    authors: Dahl J,Freund R,Blenis J,Benjamin TL

    更新日期:1996-06-01 00:00:00

  • A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells.

    abstract::The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.1.309

    authors: Nelson BH,Lord JD,Greenberg PD

    更新日期:1996-01-01 00:00:00

  • Mitochondrial Abnormality Facilitates Cyst Formation in Autosomal Dominant Polycystic Kidney Disease.

    abstract::Autosomal dominant polycystic kidney disease (ADPKD) constitutes the most inherited kidney disease. Mutations in the PKD1 and PKD2 genes, encoding the polycystin 1 and polycystin 2 Ca2+ ion channels, respectively, result in tubular epithelial cell-derived renal cysts. Recent clinical studies demonstrate oxidative stre...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00337-17

    authors: Ishimoto Y,Inagi R,Yoshihara D,Kugita M,Nagao S,Shimizu A,Takeda N,Wake M,Honda K,Zhou J,Nangaku M

    更新日期:2017-11-28 00:00:00

  • Rates of mutation to growth factor autonomy and tumorigenicity differ in hematopoietic stem and precursor cells expressing the multilineage colony-stimulating factor gene.

    abstract::At least two separate but interdependent events are required to attain autonomous growth as a consequence of ectopic expression of the multilineage colony-stimulating factor gene in hematopoietic progenitor cells. The rate at which the second event occurs is more than 3 orders of magnitude higher in precursor cell lin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.12.5746

    authors: Laker C,Kluge N,Stocking C,Just U,Franz MJ,Ostertag W,DeLamarter JF,Dexter M,Spooncer E

    更新日期:1989-12-01 00:00:00

  • Proteomics analysis reveals stable multiprotein complexes in both fission and budding yeasts containing Myb-related Cdc5p/Cef1p, novel pre-mRNA splicing factors, and snRNAs.

    abstract::Schizosaccharomyces pombe Cdc5p and its Saccharomyces cerevisiae ortholog, Cef1p, are essential Myb-related proteins implicated in pre-mRNA splicing and contained within large multiprotein complexes. Here we describe the tandem affinity purification (TAP) of Cdc5p- and Cef1p-associated complexes. Using transmission el...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.7.2011-2024.2002

    authors: Ohi MD,Link AJ,Ren L,Jennings JL,McDonald WH,Gould KL

    更新日期:2002-04-01 00:00:00

  • Enhancer blocking activity of the insulator at H19-ICR is independent of chromatin barrier establishment.

    abstract::Transcriptional insulators are cis regulatory elements that organize chromatin into independently regulated domains. At the imprinted murine Igf2/H19 locus, the H19-ICR insulator prevents the activation of the Igf2 promoter on the maternal allele by enhancers that activate H19 on the same chromosome. Given the well-de...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00091-08

    authors: Singh V,Srivastava M

    更新日期:2008-06-01 00:00:00

  • MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties.

    abstract::The human genome contains a number of methyl CpG binding proteins that translate DNA methylation into a physiological response. To gain insight into the function of MBD2 and MBD3, we first applied protein tagging and mass spectrometry. We show that MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.3.843-851.2006

    authors: Le Guezennec X,Vermeulen M,Brinkman AB,Hoeijmakers WA,Cohen A,Lasonder E,Stunnenberg HG

    更新日期:2006-02-01 00:00:00

  • Overproduction of Rb protein after the G1/S boundary causes G2 arrest.

    abstract::The Rb protein is known to exert its activity at decision points in the G1 phase of the cell cycle. To investigate whether it may also play some role(s) at later points in the cell cycle, we used a system of rapid inducible gene amplification to conditionally overexpress Rb protein during G2 phase. A cell line express...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.11.6640

    authors: Karantza V,Maroo A,Fay D,Sedivy JM

    更新日期:1993-11-01 00:00:00

  • Granulocyte-macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates myeloid progenitor cell proliferation and enhances the function of terminally differentiated effector cells. Interleukin-3 (IL-3) stimulation results in the proliferation and maturation of early bone marrow progenitor cells. These activities are medi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.9.5975

    authors: Sakamoto KM,Fraser JK,Lee HJ,Lehman E,Gasson JC

    更新日期:1994-09-01 00:00:00

  • A mutation allowing an mRNA secondary structure diminishes translation of Saccharomyces cerevisiae iso-1-cytochrome c.

    abstract::The CYC1-239-O mutation in the yeast Saccharomyces cerevisiae produces a -His-Leu- replacement of the normal -Ala-Gly- sequence at amino acid positions 5 and 6, which lie within a dispensable region of iso-1-cytochrome c; this mutation can accommodate the formation of a hairpin structure at the corresponding site in t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.8.1839

    authors: Baim SB,Pietras DF,Eustice DC,Sherman F

    更新日期:1985-08-01 00:00:00

  • Cyclin-specific control of ribosomal DNA segregation.

    abstract::Following chromosome duplication in S phase of the cell cycle, the sister chromatids are linked by cohesin. At the onset of anaphase, separase cleaves cohesin and thereby initiates sister chromatid separation. Separase activation results from the destruction of its inhibitor, securin, which is triggered by a ubiquitin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00235-08

    authors: Sullivan M,Holt L,Morgan DO

    更新日期:2008-09-01 00:00:00

  • Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family.

    abstract::A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leuci...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.12.6642

    authors: Chang CJ,Chen TT,Lei HY,Chen DS,Lee SC

    更新日期:1990-12-01 00:00:00

  • Inheritance of extrachromosomal rDNA in Physarum polycephalum.

    abstract::In the acellular slime mold Physarum polycephalum, the several hundred genes coding for rRNA are located on linear extrachromosomal DNA molecules of a discrete size, 60 kilobases. Each molecule contains two genes that are arranged in a palindromic fashion and separated by a central spacer region. We investigated how r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.4.635

    authors: Ferris PJ,Vogt VM,Truitt CL

    更新日期:1983-04-01 00:00:00

  • Genotoxic stress prevents Ndd1-dependent transcriptional activation of G2/M-specific genes in Saccharomyces cerevisiae.

    abstract::Downregulation of specific transcripts is one of the mechanisms utilized by eukaryotic checkpoint systems to prevent cell cycle progression. Here we identified and explored such a mechanism in the yeast Saccharomyces cerevisiae. It involves the Mec1-Rad53 kinase cascade, which attenuates G(2)/M-specific gene transcrip...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01090-13

    authors: Yelamanchi SK,Veis J,Anrather D,Klug H,Ammerer G

    更新日期:2014-02-01 00:00:00

  • The signal response of IkappaB alpha is regulated by transferable N- and C-terminal domains.

    abstract::IkappaB alpha retains the transcription factor NF-kappaB in the cytoplasm, thus inhibiting its function. Various stimuli inactivate IkappaB alpha by triggering phosphorylation of the N-terminal residues Ser32 and Ser36. Phosphorylation of both serines is demonstrated directly by phosphopeptide mapping utilizing calpai...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.6.3021

    authors: Brown K,Franzoso G,Baldi L,Carlson L,Mills L,Lin YC,Gerstberger S,Siebenlist U

    更新日期:1997-06-01 00:00:00

  • A novel in vivo transcription assay demonstrates the presence of globin-inducing trans-acting factors in uninduced murine erythroleukemia cells.

    abstract::We report the development of a novel in vivo transcription assay for trans-acting factors regulating the human gamma- and beta-globin genes. A cDNA coding for the human tissue-type plasminogen activator (t-PA) was inserted into the globin genes. Simian virus 40 small T-antigen splice and polyadenylation signals were i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.1.130

    authors: Wrighton N,Grosveld F

    更新日期:1988-01-01 00:00:00

  • LIM-Only Protein FHL2 Is a Negative Regulator of Transforming Growth Factor β1 Expression.

    abstract::Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of a DNA-binding domain, FH...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00636-16

    authors: Dahan J,Levillayer F,Xia T,Nouët Y,Werts C,Fanton d'Andon M,Adib-Conquy M,Cassard-Doulcier AM,Khanna V,Chen J,Tordjmann T,Buendia MA,Jouvion G,Wei Y

    更新日期:2017-05-02 00:00:00

  • Potentiation of protein kinase C zeta activity by 15-deoxy-delta(12,14)-prostaglandin J(2) induces an imbalance between mitogen-activated protein kinases and NF-kappa B that promotes apoptosis in macrophages.

    abstract::Activation of the macrophage cell line RAW 264.7 with lipopolysaccharide (LPS) transiently activates protein kinase C zeta (PKC zeta) and Jun N-terminal kinase (JNK) through a phosphoinositide-3-kinase (PI3-kinase)-dependent pathway. Incubation of LPS-treated cells with the cyclopentenone 15-deoxy-Delta(12,14)-prostag...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.4.1196-1208.2003

    authors: Castrillo A,Través PG,Martín-Sanz P,Parkinson S,Parker PJ,Boscá L

    更新日期:2003-02-01 00:00:00

  • The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6.

    abstract::In Saccharomyces cerevisiae (budding yeast), commitment to cell division in late G(1) is promoted by the G(1) cyclin Cln3 and its associated cyclin-dependent kinase, Cdc28. We show here that all known aspects of the function of Cln3 in G(1) phase, including control of cell size, pheromone sensitivity, cell cycle progr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.12.4402-4418.2002

    authors: Wijnen H,Landman A,Futcher B

    更新日期:2002-06-01 00:00:00

  • mTORC1 and -2 Coordinate Transcriptional and Translational Reprogramming in Resistance to DNA Damage and Replicative Stress in Breast Cancer Cells.

    abstract::mTOR coordinates growth signals with metabolic pathways and protein synthesis and is hyperactivated in many human cancers. mTOR exists in two complexes: mTORC1, which stimulates protein, lipid, and ribosome biosynthesis, and mTORC2, which regulates cytoskeleton functions. While mTOR is known to be involved in the DNA ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00577-16

    authors: Silvera D,Ernlund A,Arju R,Connolly E,Volta V,Wang J,Schneider RJ

    更新日期:2017-02-15 00:00:00

  • The cellular response to neuregulins is governed by complex interactions of the erbB receptor family.

    abstract::Deregulated signaling by the four members of the epidermal growth factor receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze signaling by these receptors have been hampered by the diversity of ligands and extensive interreceptor cross ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.10.5770

    authors: Riese DJ 2nd,van Raaij TM,Plowman GD,Andrews GC,Stern DF

    更新日期:1995-10-01 00:00:00

  • Yeast killer plasmid mutations affecting toxin secretion and activity and toxin immunity function.

    abstract::M double-stranded RNA (MdsRNA) plasmid mutants were obtained by mutagenesis and screening of a diploid killer culture partially heat cured of the plasmid, so that a high proportion of the cells could be expected to have only on M plasmid. Mutants with neutral (nonkiller [K-], immune [R+]) or suicide (killer [K+], sens...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.4.346

    authors: Bussey H,Sacks W,Galley D,Saville D

    更新日期:1982-04-01 00:00:00