Technicolour transgenics: imaging tools for functional genomics in the mouse

Over the past decade, a battery of powerful tools that encompass forward and reverse genetic approaches have been developed to dissect the molecular and cellular processes that regulate development and disease. The advent of genetically-encoded fluorescent proteins that are expressed in wild type and mutant mice, together with advances in imaging technology, make it possible to study these biological processes in many dimensions. Importantly, these technologies allow direct visual access to complex events as they happen in their native environment, which provides greater insights into mammalian biology than ever before.

[1]  V. Wilson,et al.  Axial progenitors with extensive potency are localised to the mouse chordoneural hinge. , 2002, Development.

[2]  Elizabeth Casey,et al.  Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. , 2001, Genetics.

[3]  A. Nagy,et al.  The orderly allocation of mesodermal cells to the extraembryonic structures and the anteroposterior axis during gastrulation of the mouse embryo. , 1999, Development.

[4]  R Y Tsien,et al.  Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Ohkura,et al.  A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein , 2001, Nature Biotechnology.

[6]  H. Niwa,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector. , 1991, Gene.

[7]  Yamamura Ken-ichi,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector , 1991 .

[8]  M E Dickinson,et al.  Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy. , 2001, BioTechniques.

[9]  J. Lichtman,et al.  In Vivo Time-Lapse Imaging of Synaptic Takeover Associated with Naturally Occurring Synapse Elimination , 2003, Neuron.

[10]  M. J. Justice,et al.  Mouse ENU mutagenesis. , 1999, Human molecular genetics.

[11]  Konstantin A Lukyanov,et al.  A strategy for the generation of non‐aggregating mutants of Anthozoa fluorescent proteins , 2002, FEBS letters.

[12]  George H. Patterson,et al.  A Photoactivatable GFP for Selective Photolabeling of Proteins and Cells , 2002, Science.

[13]  N. Heintz,et al.  Bac to the future: The use of bac transgenic mice for neuroscience research , 2001, Nature Reviews Neuroscience.

[14]  S. Fraser,et al.  Tracing transgene expression in living zebrafish embryos. , 2001, Developmental biology.

[15]  M. Ikawa,et al.  Glowing Podocytes in Living Mouse: Transgenic Mouse Carrying a Podocyte-Specific Promoter , 1999, Nephron Experimental Nephrology.

[16]  D. Piston.  Imaging living cells and tissues by two-photon excitation microscopy. , 1999, Trends in cell biology.

[17]  M. Ikawa,et al.  Alkalinization of acrosome measured by GFP as a pH indicator and its relation to sperm capacitation. , 2001, Developmental biology.

[18]  Alexandra L. Joyner,et al.  Gene targeting: a practical approach. , 1993 .

[19]  E. Batourina,et al.  Vitamin A controls epithelial/mesenchymal interactions through Ret expression , 2001, Nature Genetics.

[20]  A. Wong,et al.  Two-Photon Calcium Imaging Reveals an Odor-Evoked Map of Activity in the Fly Brain , 2003, Cell.

[21]  A. Nagy,et al.  Insufficient VEGFA activity in yolk sac endoderm compromises haematopoietic and endothelial differentiation. , 2002, Development.

[22]  R. Tsien,et al.  A monomeric red fluorescent protein , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  N. Manley,et al.  New serum‐free in vitro culture technique for midgestation mouse embryos , 2003, Genesis.

[24]  H. Schöler,et al.  The onset of germ cell migration in the mouse embryo , 2000, Mechanisms of Development.

[25]  G. Feng,et al.  Asynchronous Synapse Elimination in Neonatal Motor Units Studies Using GFP Transgenic Mice , 2001, Neuron.

[26]  J. Sanes,et al.  Pre-existing pathways promote precise projection patterns , 2002, Nature Neuroscience.

[27]  R. Behringer,et al.  The organizer of the mouse gastrula is composed of a dynamic population of progenitor cells for the axial mesoderm. , 2001, Development.

[28]  J. Lippincott-Schwartz,et al.  Studying protein dynamics in living cells , 2001, Nature Reviews Molecular Cell Biology.

[29]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[30]  B. Hogan,et al.  Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. , 2000, Development.

[31]  M. Ikawa,et al.  Efficient chromosomal transposition of a Tc1/mariner- like transposon Sleeping Beauty in mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Tessier-Lavigne,et al.  Stereotyped Pruning of Long Hippocampal Axon Branches Triggered by Retraction Inducers of the Semaphorin Family , 2003, Cell.

[33]  M E Dickinson,et al.  Dynamic in vivo imaging of postimplantation mammalian embryos using whole embryo culture , 2002, Genesis.

[34]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .

[35]  S. Lukyanov,et al.  GFP‐like chromoproteins as a source of far‐red fluorescent proteins , 2001, FEBS letters.

[36]  B. Glick,et al.  Rapidly maturing variants of the Discosoma red fluorescent protein (DsRed) , 2002, Nature Biotechnology.

[37]  J. Fetcho,et al.  In Vivo Imaging of Zebrafish Reveals Differences in the Spinal Networks for Escape and Swimming Movements , 2001, The Journal of Neuroscience.

[38]  A. Nagy,et al.  Embryonic stem cells and mice expressing different GFP variants for multiple non-invasive reporter usage within a single animal , 2002, BMC biotechnology.

[39]  R. Tsien,et al.  Fluorescent indicators for Ca2+based on green fluorescent proteins and calmodulin , 1997, Nature.

[40]  K. Anderson,et al.  Finding the genes that direct mammalian development : ENU mutagenesis in the mouse. , 2000, Trends in genetics : TIG.

[41]  Mark E Brezinski,et al.  Ultrasound induced improvement in optical coherence tomography (OCT) resolution , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Okabe,et al.  Tissue‐inherent fate of GPI revealed by GPI‐anchored GFP transgenesis , 1999, FEBS letters.

[43]  T. Magnuson,et al.  Imprinted X inactivation maintained by a mouse Polycomb group gene , 2001, Nature Genetics.

[44]  V. Papaioannou,et al.  Loss of Tbx4 blocks hindlimb development and affects vascularization and fusion of the allantois , 2003, Development.

[45]  Philippe Soriano,et al.  Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. , 1991, Genes & development.

[46]  John White,et al.  Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability , 1999, Nature Biotechnology.

[47]  M. McPherson,et al.  PCR 2 : a practical approach , 2016 .

[48]  S. Nishikawa,et al.  Chamber‐specific differentiation of Nkx2.5‐positive cardiac precursor cells from murine embryonic stem cells , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[49]  Choun-Ki Joo,et al.  Wnt/β-Catenin/Tcf Signaling Induces the Transcription of Axin2, a Negative Regulator of the Signaling Pathway , 2002, Molecular and Cellular Biology.

[50]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[51]  J. Rossant,et al.  Promotion of trophoblast stem cell proliferation by FGF4. , 1998, Science.

[52]  C. Lo,et al.  Tracking of mouse cell lineage using microinjected DNA sequences: analyses using genomic Southern blotting and tissue-section in situ hybridizations. , 1987, Differentiation; research in biological diversity.

[53]  M. J. Cormier,et al.  Primary structure of the Aequorea victoria green-fluorescent protein. , 1992, Gene.

[54]  R. Lin,et al.  The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis , 2002, The Journal of cell biology.

[55]  S. Lukyanov,et al.  Fluorescent proteins from nonbioluminescent Anthozoa species , 1999, Nature Biotechnology.

[56]  B. Weinstein.  Vascular cell biology in vivo: a new piscine paradigm? , 2002, Trends in cell biology.

[57]  L. Tsui,et al.  In situ detection of beta-galactosidase in lenses of transgenic mice with a gamma-crystallin/lacZ gene. , 1987, Science.

[58]  D. Turnbull,et al.  Ultrasound backscatter microscopy of mouse embryos. , 2000, Methods in molecular biology.

[59]  M. Doughty,et al.  BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin , 1999, Nature Genetics.

[60]  T. Kanda,et al.  Histone–GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells , 1998, Current Biology.

[61]  K. J. Sepp,et al.  RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia , 2003, Development.

[62]  J. Campos-Ortega,et al.  A zebrafish histone variant H2A.F/Z and a transgenic H2A.F/Z:GFP fusion protein for in vivo studies of embryonic development , 2001, Development Genes and Evolution.

[63]  M. Dyer,et al.  Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. , 2001, Development.

[64]  S J Remington,et al.  Refined crystal structure of DsRed, a red fluorescent protein from coral, at 2.0-A resolution. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[65]  S. P. Beddington.  An autoradiographic analysis of the potency of embryonic ectoderm in the 8th day postimplantation mouse embryo. , 1981, Journal of embryology and experimental morphology.

[66]  G. Feng,et al.  Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP , 2000, Neuron.

[67]  Shiaoching Gong,et al.  Highly efficient modification of bacterial artificial chromosomes (BACs) using novel shuttle vectors containing the R6Kgamma origin of replication. , 2002, Genome research.

[68]  T. Sadler,et al.  Culture of mouse embryos during neurulation. , 1981, Journal of embryology and experimental morphology.

[69]  P. Stambrook,et al.  Reporter genes in transgenic mice , 1994, Transgenic Research.

[70]  B. Sauer,et al.  Conditional gene knockout using Cre recombinase. , 2001, Molecular biotechnology.

[71]  T Wilson,et al.  The theory of the direct‐view confocal microscope , 1981, Journal of microscopy.

[72]  D. Beier,et al.  ENU Mutagenesis in the Mouse , 2003, Current protocols in human genetics.

[73]  Steve D. M. Brown,et al.  A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse , 2000, Nature Genetics.

[74]  Tomoko Nakanishi,et al.  ‘Green mice’ as a source of ubiquitous green cells , 1997, FEBS letters.

[75]  M. Lewandoski.  Conditional control of gene expression in the mouse , 2001, Nature Reviews Genetics.

[76]  R. Jaenisch,et al.  X-Chromosome inactivation in cloned mouse embryos. , 2000, Science.

[77]  Takeharu Nagai,et al.  Shift anticipated in DNA microarray market , 2002, Nature Biotechnology.

[78]  A. Szalay,et al.  A Renilla luciferase-Aequorea GFP (ruc-gfp) fusion gene construct permits real-time detection of promoter activation by exogenously administered mifepristone in vivo , 2002, Molecular Genetics and Genomics.

[79]  W. Stanford,et al.  Gene-trap mutagenesis: past, present and beyond , 2001, Nature Reviews Genetics.

[80]  P. Devreotes,et al.  Receptor-Mediated Activation of Heterotrimeric G-Proteins in Living Cells , 2001, Science.

[81]  G. Bearman,et al.  Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy. , 2001, Journal of biomedical optics.

[82]  B. Sauer,et al.  Brief expression of a GFP cre fusion gene in embryonic stem cells allows rapid retrieval of site-specific genomic deletions. , 1997, Nucleic acids research.

[83]  K. Svoboda,et al.  Photon Upmanship: Why Multiphoton Imaging Is More than a Gimmick , 1997, Neuron.

[84]  T. Graf,et al.  Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. , 2000, Blood.

[85]  Steve M. Potter,et al.  Structure and Emergence of Specific Olfactory Glomeruli in the Mouse , 2001, The Journal of Neuroscience.

[86]  R. Balling,et al.  Systematic approaches to mouse mutagenesis. , 2001, Current opinion in genetics & development.

[87]  S Falkow,et al.  FACS-optimized mutants of the green fluorescent protein (GFP). , 1996, Gene.

[88]  Ronald L. Davis,et al.  Detection of Calcium Transients in DrosophilaMushroom Body Neurons with Camgaroo Reporters , 2003, The Journal of Neuroscience.

[89]  R. Beddington,et al.  Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo , 1996, Current Biology.

[90]  Janet Rossant,et al.  Direct Neural Fate Specification from Embryonic Stem Cells A Primitive Mammalian Neural Stem Cell Stage Acquired through a Default Mechanism , 2001, Neuron.

[91]  Caiying Guo,et al.  Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon cre‐mediated excision , 2000, Genesis.

[92]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[93]  Klaus Schughart,et al.  Genome-wide, large-scale production of mutant mice by ENU mutagenesis , 2000, Nature Genetics.

[94]  S. Fraser,et al.  Direct imaging of in vivo neuronal migration in the developing cerebellum , 2001, Current Biology.

[95]  David J. Anderson,et al.  The bHLH Transcription Factors OLIG2 and OLIG1 Couple Neuronal and Glial Subtype Specification , 2002, Cell.

[96]  Roger Y. Tsien,et al.  Creating new fluorescent probes for cell biology , 2003, Nature Reviews Molecular Cell Biology.

[97]  E. Batourina,et al.  Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret , 2002, Nature Genetics.

[98]  R. Tsien,et al.  Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer , 1996, Current Biology.

[99]  A Miyawaki,et al.  Directed evolution of green fluorescent protein by a new versatile PCR strategy for site-directed and semi-random mutagenesis. , 2000, Nucleic acids research.

[100]  M. Dickinson,et al.  Dorsalization of the neural tube by the non-neural ectoderm. , 1995, Development.

[101]  L A Herzenberg,et al.  Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[102]  J. Rossant,et al.  Chimeras and mosaics in mouse mutant analysis. , 1998, Trends in genetics : TIG.

[103]  A Miyawaki,et al.  Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[104]  S. Martinez,et al.  Mammalian neural tube grafting experiments: an in vitro system for mouse experimental embryology. , 2001, The International journal of developmental biology.

[105]  J. Biggers,et al.  Development of Mouse Embryos in vivo after Cultivation from Two-cell Ova to Blastocysts in vitro , 1965, Nature.

[106]  A. Nagy,et al.  FACS for the isolation of individual cells from transgenic mice harboring a fluorescent protein reporter , 2000, Genesis.

[107]  C. Rieder,et al.  Mitosis in primary cultures of Drosophila melanogaster larval neuroblasts. , 2002, Journal of cell science.

[108]  A. Nagy,et al.  An X‐linked GFP transgene reveals unexpected paternal X‐chromosome activity in trophoblastic giant cells of the mouse placenta , 2001, Genesis.

[109]  Fritjof Helmchen,et al.  Miniaturization of Fluorescence Microscopes Using Fibre Optics , 2002, Experimental physiology.

[110]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[111]  S. Kain,et al.  Generation of Destabilized Green Fluorescent Protein as a Transcription Reporter* , 1998, The Journal of Biological Chemistry.

[112]  Roger Y. Tsien,et al.  Seeing the Machinery of Live Cells , 1998, Science.

[113]  S. Goldman,et al.  Isolation of neuronal precursors by sorting embryonic forebrain transfected with GFP regulated by the Tα1 tubulin promoter , 1998, Nature Biotechnology.

[114]  M. Ikawa,et al.  Non-invasive sexing of preimplantation stage mammalian embryos , 1998, Nature Genetics.

[115]  K. Anderson,et al.  The transformation of the model organism: a decade of developmental genetics , 2003, Nature Genetics.

[116]  I. Rodriguez,et al.  Variable Patterns of Axonal Projections of Sensory Neurons in the Mouse Vomeronasal System , 1999, Cell.

[117]  G. Schultz,et al.  Roles of Gβγ in membrane recruitment and activation of p110γ/p101 phosphoinositide 3-kinase γ , 2003, The Journal of cell biology.

[118]  M. Chalfie.  GREEN FLUORESCENT PROTEIN , 1995, Photochemistry and photobiology.

[119]  A. Miyawaki,et al.  An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[120]  R. Saint,et al.  A His2AvDGFP fusion gene complements a lethal His2AvD mutant allele and provides an in vivo marker for Drosophila chromosome behavior. , 1999, DNA and cell biology.

[121]  Jaime Grutzendler,et al.  Rapid labeling of neuronal populations by ballistic delivery of fluorescent dyes. , 2003, Methods.

[122]  J. Nichols,et al.  Embryonic stem cells and transgenic mice ubiquitously expressing a tau-tagged green fluorescent protein. , 2000, Developmental biology.

[123]  N. Perrimon,et al.  Tailoring the genome: the power of genetic approaches , 2003, Nature Genetics.

[124]  V. D’Agati,et al.  Expression of green fluorescent protein in the ureteric bud of transgenic mice: a new tool for the analysis of ureteric bud morphogenesis. , 1999, Developmental genetics.

[125]  R. Hynes,et al.  Mouse primordial germ cells lacking beta1 integrins enter the germline but fail to migrate normally to the gonads. , 1999, Development.

[126]  H. Okano,et al.  Promoter‐targeted selection and isolation of neural progenitor cells from the adult human ventricular zone , 2000, Journal of neuroscience research.

[127]  Shankar Srinivas,et al.  Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus , 2001, BMC Developmental Biology.

[128]  Scott E Fraser,et al.  Multiphoton excitation spectra in biological samples. , 2003, Journal of biomedical optics.

[129]  J. Biggers,et al.  Differential growth of the mouse preimplantation embryo in chemically defined media. , 1994, Biology of reproduction.

[130]  E. Gahtan,et al.  Probing neural circuits in the zebrafish: a suite of optical techniques. , 2003, Methods.

[131]  M. Ikawa,et al.  Generating green fluorescent mice by germline transmission of green fluorescent ES cells , 1998, Mechanisms of Development.

[132]  Paul Martin,et al.  Dynamic Analysis of Actin Cable Function during Drosophila Dorsal Closure , 2002, Current Biology.

[133]  R Y Tsien,et al.  Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[134]  Winfried Denk,et al.  New developments in multiphoton microscopy , 2002, Current Opinion in Neurobiology.

[135]  J. Lippincott-Schwartz,et al.  Development and Use of Fluorescent Protein Markers in Living Cells , 2003, Science.

[136]  J. Rossant,et al.  Anterior mesendoderm induces mouse Engrailed genes in explant cultures. , 1993, Development.

[137]  R. Tsien,et al.  Reducing the Environmental Sensitivity of Yellow Fluorescent Protein , 2001, The Journal of Biological Chemistry.

[138]  Dai Fukumura,et al.  Dissecting tumour pathophysiology using intravital microscopy , 2002, Nature Reviews Cancer.

[139]  A. Bradley,et al.  Engineering chromosomal rearrangements in mice , 2001, Nature Reviews Genetics.

[140]  A. Hadjantonakis,et al.  Can mammalian cloning combined with embryonic stem cell technologies be used to treat human diseases? , 2002, Genome Biology.