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26 Thomas, Kirk R.; Capecchi, Mario R.Nonreciprocal exchanges of information between DNA duplexes coinjected into mammalian. cell nucleiWe have examined the mechanism of homologous recombination between plasmid molecules coinjected into cultured mammalian cells. Cell lines containing recombinant DNA molecules were obtained by selecting for the reconstruction of a functional Neor gene from two plasmids that bear different amber mutat...Animals; Cells, Cultured; DNA Restriction Enzymes; Kinetics1985-01
27 Thomas, Kirk R.; Capecchi, Mario R.Efficient correction of mismatched bases in plasmid heteroduplexes injected into cultured mammalian cell nuclei.Heteroduplexes were prepared from two plasmids, pRH4-14/TK and pRH5-8/TK, containing different amber mutations in the neomycin resistance gene (Neor). The Neor gene was engineered to be expressed in both bacterial and mammalian cells. A functional Neor gene conferred kanamycin resistance to bacteria...Cell Nucleus; Cells, Cultured; Microinjections1985-01
28 Capecchi, Mario R.Expression of a microinjected porcine class I major histocompatibility complex gene in transgenic mice.A porcine class I major histocompatibility complex (SLA) gene has been introduced into the genome of a C57BL/10 mouse. This transgenic mouse expressed SLA antigen on its cell surfaces and transmitted the gene to offspring, in which the gene is also expressed. Skin grafts of such transgenic mice were...Genetic Engineering; Graft Rejection; Mice, Inbred C57BL1985-05-03
29 Capecchi, Mario R.Isolation and characterization of Caenorhabditis elegans DNA sequences homologous to the v-abl oncogene.DNA sequences homologous to the v-abl oncogene were isolated from a Caenorhabditis elegans genomic library by their ability to hybridize with a v-src probe. The DNA sequence of 2465 nucleotides of one clone was determined. This region corresponds to the 5' protein kinase domain of v-abl plus approxi...Amino Acid Sequence; Animals; Base Sequence; Gene Expression Regulation; Transcription, Genetic1986-04
30 Capecchi, Mario R.Homologous recombination between coinjected DNA sequences peaks in early to mid-S phase.We have examined the effect of cell cycle position on homologous recombination between plasmid molecules coinjected into synchronized rat fibroblasts. Recombination activity was found to be low in G1 and to rise 10- to 15-fold, peaking in early to mid-S phase.Cell Line; Kinetics; Plasmids1986-06
31 Thomas, Kirk R.; Capecchi, Mario R.Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene.Injection of homologous DNA sequences into nuclei of cultured mammalian cells induces mutations in the cognate chromosomal gene. It appears that these mutations result from incorrect repair of a heteroduplex formed between the introduced and the chromosomal sequence. This phenomenon is termed 'heter...Animals; Cell Line; Drug Resistance, Microbial; Fibroblasts; Mice; Models, Genetic; Neomycin; Plasmids1986-11-06
32 Gesteland, Raymond F.; Atkins, John F.; Weiss, Robert B.Slippery runs, shifty stops, backward steps and forward hops: -2, -1, +1, +2, +5 and +6 Ribosomal frameshiftingFrameshift mutations frequently express residual levels of gene activity; that is, they are often leaky. This leakiness can be used as a tool to define the functional components that affect the reading frame during gene expression. Recent technological advances in the capability to efficiently bu...Molecular Sequence Data; Mutation; RNA, Transfer; Frameshifting1987
33 Capecchi, Mario R.; Mansour, Suzanne L.; Thomas, Kirk R.Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes.Gene targeting--homologous recombination of DNA sequences residing in the chromosome with newly introduced DNA sequences--in mouse embryo-derived stem cells promises to provide a means to generate mice of any desired genotype. We describe a positive nd negative selection procedure that enriches 2,00...Animals; Clone Cells; Restriction Mapping; Stem Cells1988-11-24
34 Baehr, WolfgangHuman interstitial retinoid-binding protein. Gene structure and primary structureInterstitial retinoid-binding protein (IRBP) is synthesized and secreted by rod photoreceptor cells into the interphotoreceptor matrix and is known to bind retinoids and fatty acids. We have used cDNA clones encoding human IRBP to isolate a 15-kilobase genomic fragment that encompasses the complete ...Molecular Sequence Data; Eye Proteins; Retinol-Binding Proteins; Messenger RNA1989-05-15
35 Capecchi, Mario R.Gene targeting: tapping the cellular telephone.Gene targeting means that we now have the potential to generate mice of virtually any desired genotype. In the first instance, standards recombinant DNA technology is used to alter a cloned DNA sequence of a chosen locus; the modified potent stem cell derived from a mouse embryo, and homologous reco...Animals; Blotting, Southern; Bone and Bones; Gene Targeting; Genotype; Immunochemistry; In Situ Hybridization; Mice1990-03-08
36 Baehr, WolfgangTissue-specific expression in transgenic mice directed by the 5'-flanking sequences of the human gene encoding interphotoreceptor retinoid-binding proteinInterphotoreceptor retinoid-binding protein (IRBP) is an extracellular protein that has been suggested to participate in the visual process as a carrier for visual retinoids. A chimeric gene composed of the human IRBP promoter fused to the bacterial reporter gene chloramphenicol acetyltransferase (C...Restriction Mapping; Nucleic Acid Hybridization; Mice; Gene Expression1990-05-25
37 Thomas, Kirk R.; Capecchi, Mario R.Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development.The int-1 proto-oncogene was first identified as a gene activated in virally induced mouse mammary tumours. Expression studies, however, suggest that the normal function of this gene may be in spermatogenesis and in the development of the central nervous system. Genes sharing sequence similarity wit...Animals; Blastocyst; Cell Line; Chimera; DNA; Female; Genotype; Heterozygote; Homozygote; Male; Mice, Inbred C57BL; Motor Activity1990-08-30
38 Mansour, Suzanne L.; Thomas, Kirk R.; Capecchi, Mario R.Introduction of a lacZ reporter gene into the mouse int-2 locus by homologous recombination.We demonstrate that the frequency of gene targeting is unaffected by the length of nonhomologous DNA transferred to a target chromosomal sequence. A result of this finding is that a much wider spectrum of designed genomic alterations is now feasible. As a first application, we inserted a 5.4-kilobas...Blotting, Southern; Cell Differentiation; Fluorescent Antibody Technique; Restriction Mapping1990-10
39 Capecchi, Mario R.Gene targeting. How efficient can you get?With targeting in Leishmania and Trypanosoma, there are now greater incentives to develop the technology in organisms of intermediate complexity such as Caenorhabditis elegans and Drosophila. The ratio of homologous to nonhomologus recombination in these organisms might prove to be greater than in m...Animals; DNA Mutational Analysis; Recombination, Genetic1990-11-08
40 Gesteland, Raymond F.; Atkins, John F.Frameshifting in gene 10 of bacteriophage T7Gene 10 of bacteriophage T7, which encodes the most abundant capsid protein, has two products: a major product, 10A (36 kDa), and a minor product, 10B (41 kDa). 10B is produced by frameshifting into the -1 frame near the end of the 10A coding frame and is incorporated into the capsid. The frameshift...Frameshifting; Bacteriophage T7; RNA, Viral; Gene Expression1991
41 Capecchi, Mario R.Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5.Gene targeting in mouse embryo-derived stem cells has been used to disrupt the homeobox gene hox-1.5. Mice heterozygous at the hox-1.5 locus appear normal, whereas hox-1.5-/hox-1.5- mice die at or shortly after birth. These homozygotes are athymic, aparathyroid, have reduced thyroid and submaxillary...Abnormalities, Multiple; Animals, Newborn; Arteries; Bone and Bones; Cartilage; Esophagus; Gene Expression; Heart Defects, Congenital; Organ Specificity; Parathyroid Glands; Pharynx; Thymus Gland; Thyroid Gland; Trachea1991-04-11
42 Capecchi, Mario R.Lessons from angiotensin-converting enzyme-deficient mice.Mice which lack ACE have low systolic blood pressure, reduced male fertility and a renal abnormality characterized by medullary hypoplasia and the inability to concentrate urine. The diverse phenotypes caused by inactivation of a single gene emphasize the many functional roles of ACE and the renin-q...Blood Pressure; Cell Line;Fertility; Kidney; Testis1991-11-01
43 Capecchi, Mario R.Creating mice with targeted disruptions in protooncogenes and homeobox genes, NIH Director's Lecture given May 21, 1992This is an audio transcript of a 1 hour, 2 minutes and 12 seconds lecture given at the National Institutes of Health by Mario Capecchi on 1992/05/21. Beginning with a short summary of the mechanics of gene transfer and the ability to create germline chimera with mutations that become hereditary wit...Transgenic mice; Gene targeting; Genetic engineering; Molecular genetics; Mutagenesis; Homeobox genes; Histology - Pathological; Gene expression; Gene regulation; Genotype; Phenotype1992
44 KSL News clip of Mario Capecchi receiving the National Medal of Science for 1991This 1 minute, 44 seconds news clip from Salt Lake City's KSLTV, Channel 5 shows Mario Capecchi receiving the National Medal of Science for 1991 from President George W. Bush at the June 13, 2002 awards ceremony. The medal was presented for Capecchi's work in genetics and his development of the pro...Transgenic mice; Gene targeting; Capecchi, Mario R.; Science - Awards - United States; Television broadcasting of news1992-06
45 Thomas, Kirk R.; Capecchi, Mario R.High-fidelity gene targeting in embryonic stem cells by using sequence replacement vectors.Mutations were targeted to the Hprt locus in murine embryonic stem cells by using sequence replacement vectors. When the vector was designed such that the mutated sequences were flanked on both sides by several kilobases of DNA homologous to the target locus, replacement of chromosomal sequences wit...Drug Resistance; Gene Rearrangement; Gentamicins1992-07
46 Capecchi, Mario R.Reexamination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus.Mutations were targeted to the Hprt locus of mouse embryo-derived stem cells by using 22 different sequence replacement and sequence insertion vectors. The targeting frequency was examined at two sites within the Hprt locus as a function of the extent of homology between the targeting vector and the...Cell Line; DNA Transposable Elements; Embryo; Exons; Mice1992-08-12
47 Thomas, Kirk R.; Capecchi, Mario R.Location of crossovers during gene targeting with insertion and replacement vectors.Gene targeting was used to introduce nonselectable genetic changes into chromosomal loci in mouse embryo-derived stem cells. The nonselectable markers were linked to a selectable marker in both insertion- and replacement-type vectors, and the transfer of the two elements to the Hprt locus was assaye...Genetic Vectors; Molecular Sequence Data; Restriction Mapping1993-04
48 Gesteland, Raymond F.; Weiss, Robert B.Efficient shine- Dalgarno sequence but not translation is necessary for LacZ mRNA stability in Escherichia coliThe 5' ends of many bacterial transcripts are important in determining mRNA stability. A series of Shine-Dalgarno (SD) sequence changes showed that the complementarity of the SD sequence to the anti-SD sequence of 16S rRNA correlates with lacZ mRNA stability in Escherichia coli. Several initiation c...Protein Biosynthesis; Ribosomes; Escherichia coli; Shine-Dalgarno Sequence1994
49 Gesteland, Raymond F.; Ives, Jeffrey T.; Stockham, Thomas G.Automated film reader for DNA sequencing based on homomorphic deconvolutionAn automated reader for electrophoresis based DNA sequencing methods is described that provides fast and accurate sequence determination. Digitized sequencing lanes are processed with homomorphic blind deconvolution in preparation for peak detection, interlane alignment, peak refinement and base cal...Sequence Analysis; Electrophoresis; Automated Film Reader; Homomorphic Deconvolution1994
50 Gesteland, Raymond F.; Atkins, John F.; Tuohy, Therese M.Uninterrupted translation through putative 12-nucleotide coding gap in sequence of carA: business as usualPrevious work of others reported an untranslated stretch of 12 nucleotides in the 5' coding sequence of carA from Pseudomonas aeruginosa. However, N-terminal protein sequencing of carA-lacZ translational fusions shows that these 12 nucleotides are normally translated in a continuous triplet manner, ...Base Sequence; Protein Biosynthesis; Sequence Deletion1994
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