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1 Kerber, Richard A.A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional lociBackground: Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success. Methodology/Principal Findings: We identified individuals from a large multigenerational population database (the Utah Populati...2012-01-01
2 AAMC Award for Distinguished Research presentation for 1998This is a 3 minutes, 51 seconds video of the presentation of the American Association of Medical Colleges' Award for Distinguished Research to Mario Capecchi and Oliver Smithies for their independent work as pioneers in gene targeting.Transgenic mice; Gene targeting; Genetic engineering; Mutagenesis; Capecchi, Mario R.; Science - Awards - United States; Smithies, Oliver; Awards presentations1998
3 Capecchi, Mario R.Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11.Mice with targeted disruptions in Hox genes have been generated to evaluate the role of the Hox complex in determining the mammalian body plan. This complex of 38 genes encodes transcription factors that specify regional information along the embryonic axes. Early in vertebrate evolution an ancestra...Alleles; Animals; Bone and Bones; Carpal Bones2003-09-02
4 Albert Lasker Awards Ceremony, 2001This is the 1 hour, 45 minutes, and 41 seconds video of the Lasker Awards Ceremony and Banquet held in September, 2001. The Albert Lasker Award for Basic Medical Research was given to Mario R. Capecchi, Oliver Smithies, and Martin Evans for their work in genetic research. Martin Evans discovered h...Capecchi, Mario R.; Gene targeting; Embryonic stem cells; Transgenic mice; Genetic engineering; Science - Awards - United States; Smithies, Oliver; Evans, Martin J.; Awards presentations2001
5 Capecchi, Mario R.Altered enzymes in drug-resistant variants of mammalian tissue culture cells.Two selective procedures are compared in an effort to isolate variants of mouse L cells containing structural gene mutations. Among the resulting variant cloned cell lines are found two types of alterations in theenzyme hypoxanthine phosphoribosyl transferase (EC 2.4.2.8.) (1): enzyme with altered ...Drug Resistance; Azaguanine; Clone Cells; Hypoxanthines1973-11
6 Coffin, Cheryl M.; Capecchi, Mario R.Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function.Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer for which outcomes are poor when the disease is advanced. Although well-developed mouse models exist for embryonal and pleomorphic rhabdomyosarcomas, neither a spontaneous nor a transgenic mouse model of alveolar rhabdomyosarcoma has...Cell Differentiation; Forkhead Transcription Factors; Myogenic Regulatory Factors2004-11-01
7 Capecchi, Mario R.Characterization of three proteins involved in polypeptide chain termination.At each stage of elongation, the growing polypeptide chain is bound to the ribosome-messenger RNA complex through the transfer RNA of the most recently incorporated amino acid residue. When the chain is complete, the last polypeptide-transfer RNA (tuna) ester linkage is cleaved, releasing the chain ...Anti-Bacterial Agents; Phenylalanine; Stimulation, Chemical1969
8 Capecchi, Mario R.Choose your target.The technology of modifying endogenous genes has recently been extended from mice to Drosophila and sheep. Concurrently, genomic sequencing is uncovering thousands of previously uncharacterized genes. Armed with today's technologies, what are our best options for delineating the functions of these n...Animals; Mice; Sheep2000-09-13
9 Capecchi, Mario R.Cleft palate in mice with a targeted mutation in the gamma-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67.The functions of neurotransmitters in fetal development are poorly understood. Genetic observations have suggested a role for the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) in the normal development of the mouse palate. Mice homozygous for mutations in the beta-3 GABAA rec...Animals, Newborn; Crosses, Genetic1997-10-14
10 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
11 Capecchi, Mario R.Critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in miceAngiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used ta...Blood pressure; ACE activity; Enzyme1997-03-06
12 Capecchi, Mario R.Detection of targeted GFP-Hox gene fuogenesissions during mouse embry.The ability to use a vital cell marker to study mouse embryogenesis will open new avenues of experimental research. Recently, the use of transgenic mice, containing multiple copies of the jellyfish gene encoding the green fluorescent protein (GFP), has begun to realize this potential. Here, we show ...Chimera; Crosses, Genetic; Gestational Age; Green Fluorescent Proteins; Mice, Inbred C57BL; Phenotype1998-10-27
13 Capecchi, Mario R.Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6.Gene targeting in mouse embryo-derived stem cells has been used to generate mice with a disruption in the homeobox gene Hox-1.6. Mice heterozygous at the Hox-1.6 locus appear normal, whereas Hox-1.6-/Hox-1.6- mice die at or shortly after birth. These homozygotes exhibit profound defects in the forma...Chromosome Mapping; Genetic Vectors; Mice, Inbred C57BL2002-06-27
14 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
15 Capecchi, Mario R.Duplication of the Hoxd11 gene causes alterations in the axial and appendicular skeleton of the mouse.The Hox genes encode a group of transcription factors essential for proper development of the mouse. Targeted mutation of the Hoxd11 gene causes reduced male fertility, vertebral transformation, carpal bone fusions, and reductions in digit length. A duplication of the Hoxd11 gene was created with th...Animals; Bone Development; Forelimb; Gene Expression Regulation, Developmental2002-09-01
16 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
17 Capecchi, Mario R.Establishment of mammalian cell lines containing multiple nonsense mutations and functional suppressor tRNA genes.We describe the generation of mammalian cell lines carrying amber suppressor genes. Nonsense mutants in the herpes simplex virus thymidine kinase (HSV tk) gene, the Escherichia coli xanthine-guanine phosphoribosyl transferase (Eco-gpt) gene and the aminoglycoside 3' phosphotransferase gene of the Tn...Cercopithecus aethiops; Escherichia coli; Xenopus1982-11-30
18 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
19 Moon, Ann M.; Capecchi, Mario R.Fgf8 is required for outgrowth and patterning of the limbs.The expression pattern and activity of fibroblast growth factor-8 (FGF8) in experimental assays indicate that it has important roles in limb development, but early embryonic lethality resulting from mutation of Fgf8 in the germ line of mice has prevented direct assessment of these roles. Here we rep...Animals; Body Patterning; Bone Morphogenetic Proteins; Ectoderm2000-12-26
20 Franklin Institute award dinner and ceremony held May 1, 1997This is a 1 hour, 42 minutes, 53 seconds video of the 1997 Franklin Institute Awards Banquet and Ceremony. The awards included a summary of each winner's achievements, the presentation of the award, and an acceptance speech. The award winners included Ralph L. Brinster, the Bower Award and Prize f...Transgenic mice; Gene targeting; Genetic engineering; Molecular genetics; Mutagenesis; Homeobox genes; Histology - Pathological; Gene expression; Gene regulation; Genotype; Phenotype1997
21 Capecchi, Mario R.Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein.The 180-amino acid core of the TATA-binding protein (TBPcore) is conserved from Archae bacteria to man. Vertebrate TBPs contain, in addition, a large and highly conserved N-terminal region that is not found in other phyla. We have generated a line of mice in which the tbp allele is replaced with a v...Mice, Knockout; Cells, Cultured; Fibroblasts; Embryo2003-02-21
22 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
23 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
24 Capecchi, Mario R.Generating mice with targeted mutations.Mutational analysis is one of the most informative approaches available for the study of complex biological processes. It has been particularly successful in the analysis of the biology of bacteria, yeast, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Extension ...Animals; Recombination, Genetic; Stem Cells2001-10-01
25 Capecchi, Mario R.Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation.hoxb-5 and hoxb-6 are adjacent genes in the mouse HoxB locus and are members of the homeotic transcription factor complex that governs establishment of the mammalian body plan. To determine the roles of these genes during development, we generated mice with a targeted disruption in each gene. Three ...Alleles; CCAAT-Enhancer-Binding Proteins; Cervical Vertebrae; DNA-Binding Proteins; Forelimb; Genetic Complementation Test1995-01-01
26 Genetics in Utah : NPR talk of the nation, science Friday for May 15, 1998This is a 1 hour, 9 seconds audio transcript of National Public Radio's Science Friday that was taped at Westminster College of Salt Lake on 1998/05/15. The host, Ira Flatow, leads a panel composed of University of Utah scientists and researchers, Jeffrey Bodkin, Mario Capecchi, Ray Gesteland, Mark...Genetic engineering; Molecular genetics; Capecchi, Mario R.; Homeobox genes; Science - Moral and ethical aspects; Human chromosome abnormalities - Diagnosis1998
27 Huang, Lin EricHIF-1? mediates tumor hypoxia to confer a perpetual mesenchymal phenotype for malignant progressionAlthough tumor progression involves genetic and epigenetic alterations to normal cellular biology, the underlying mechanisms of these changes remain obscure. Numerous studies have shown that hypoxia-inducible factor 1? (HIF-1?) is overexpressed in many human cancers and up-regulates a host of hypoxi...
28 Capecchi, Mario R.High efficiency transformation by direct microinjection of DNA into cultured mammalian cells.Direct microinjection of DNA by glass micropipettes was used to introduce the Herpes simplex virus thymidine kinase gene into cultured mammalian cells. When DNA was delivered directly into the nuclei of LMTK-, a mouse cell line deficient in thymidine kinase activity, 50--100% of the cells expressed ...Cell Nucleus; Cytoplasm; DNA, Viral; Microinjections; Recombination, Genetic1980-11-22
29 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
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 Capecchi, Mario R.Housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland.Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism occurring in most cell types. However, this housekeeping gene is expressed at very high levels in a number of mammalian tissues including the lactating mammary epithelium, suggesting additional roles for XOR in these tiss...Body Weight; Cell Differentiation; Cell Membrane; Epithelium2002-12-15
32 Capecchi, Mario R.How close are we to implementing gene targeting in animals other than the mouse?Describes several significant contributions that bring us much closer to extending ‘‘gene targeting'' to mammalian species other than the mouse. Gene targeting now provides the means for creating new strains of mice with mutations in virtually any gene. First, the desired mutation is introduced ...Cattle; Mutagenesis; Mice; Humans; Ethics, Medical2000-02-01
33 Capecchi, Mario R.Hox genes and mammalian developmentWe have examined the interactions of Hox genes in forming a cervical vertebrae, hindbrain, and limbs. In each case, it is apparent that individual Hox genes are performing individual functions but that more profound roles are apparent when they act in combination with others Hox genes. The observed ...Drosophila; Gene Expression Regulation, Developmental; Homozygote1997
34 Capecchi, Mario R.Hox group 3 paralogous genes act synergistically in the formation of somitic and neural crest-derived structures.Hox genes encode transcription factors that are used to regionalize the mammalian embryo. Analysis of mice carrying targeted mutations in individual and multiple Hox genes is beginning to reveal a complex network of interactions among these closely related genes which is responsible for directing th...Abnormalities, Multiple; Gene Targeting; Glossopharyngeal Nerve; Mice, Knockout; Morphogenesis1997-12-15
35 Capecchi, Mario R.Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands.The thymus, thyroid, and parathyroid glands in vertebrates develop from the pharyngeal region, with contributions both from pharyngeal endoderm and from neural crest cells in the pharyngeal arches. Hoxa3 mutant homozygotes have defects in the development of all three organs. Roles for the Hoxa3 para...Animals, Newborn; Calcitonin; Ectoderm; Gene Dosage; Genotype; Mice, Mutant Strains; Phenotype1998-03-01
36 Capecchi, Mario R.Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton.Mice in which all members of the Hox10 or Hox11 paralogous group are disrupted provide evidence that these Hox genes are involved in global patterning of the axial and appendicular skeleton. In the absence of Hox10 function, no lumbar vertebrae are formed. Instead, ribs project from all posterior ve...Alleles; Animals; Forelimb; Gene Expression Regulation, Developmental; Hindlimb2003-07-18
37 Capecchi, Mario R.Hox11 paralogous genes are essential for metanephric kidney inductionThe mammalian Hox complex is divided into four linkage groups containing 13 sets of paralogous genes. These paralogous genes have retained functional redundancy during evolution. For this reason, loss of only one or two Hox genes within a paralogous group often results in incompletely penetrant phen...Metanephric; Six2; Wt12002-06-01
38 Capecchi, Mario R.; Tvrdik, PetrHoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry.Formation of neuronal circuits in the head requires the coordinated development of neurons within the central nervous system (CNS) and neural crest-derived peripheral target tissues. Hoxb1, which is expressed throughout rhombomere 4 (r4), has been shown to be required for the specification of facial...Rhombomere 4; Branchiomotor; Cranial Nerve2004-07-04
39 Capecchi, Mario R.Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebraeTo address the expression and function of Hoxb13, the 5' most Hox gene in the HoxB cluster, we have generated mice with loss-of-function and beta-galactosidase reporter insertion alleles of this gene. Mice homozygous for Hoxb13 loss-of-function mutations show overgrowth in all major structures deriv...Animals; Axons; Ganglia, Spinal; Mice; Spinal Cord2003-04-15
40 Capecchi, Mario R.Hoxb8 is required for normal grooming behavior in mice.Repertoires of grooming behaviors critical to survival are exhibited by most animal species, including humans. Genes that influence this complex behavior are unknown. We report that mice with disruptions of Hoxb8 show, with 100% penetrance, excessive grooming leading to hair removal and lesions. Add...Aging; Alleles; Animals, Newborn; Behavior, Animal; Bone and Bones; Disease Models, Animal; Mice, Knockout Nerve Net2002-01-03
41 Capecchi, Mario R.Hoxc13 mutant mice lack external hairHox genes are usually expressed temporally and spatially in a colinear manner with respect to their positions in the Hox complex. Consistent with the expected pattern for a paralogous group 13 member, early embryonic Hoxc13 expression is found in the nails and tail. Hoxc13 is also expressed in vibri...Filiform papillae; Homozygotes; Paralogous1998-01-01
42 Capecchi, Mario R.Illegitimate cre-dependent chromosome rearrangements in transgenic mouse spermatids.The bacteriophage P1 Cre/loxP system has become a powerful tool for in vivo manipulation of the genomes of transgenic mice. Although in vitro studies have shown that Cre can catalyze recombination between cryptic "pseudo-loxP" sites in mammalian genomes, to date there have been no reports of loxP-si...Chromatin; Female; Mice, Inbred C57BL; Phenotype2000-12-05
43 Capecchi, Mario R.In vivo and in vitro tissue-specific expression of green fluorescent protein using the cre-lox system in mouse embryonic stem cells.Embryonic stem cells (ES) are pluripotent and may therefore serve as a source for the generation of specific cell types required for future therapies based on cell replacement. The isolation of defined cell populations from a certain lineage or tissue is a prerequisite for the analysis of the potent...Animals; Cell Differentiation; Cells, Cultured; Gene Transfer Techniques; Mice, Transgenic2005-10-23
44 Capecchi, Mario R.Initiation of E. coli proteins.Recent experiments and theoretical arguments suggest that formylmethionyl sRNA is employed as an initiator of protein synthesis. Studies also indicated that other phage proteins synthesized in the in vitro system were initiated with formylmethionine. These observations provided a basis for believin...Alanine; Chromatography, Paper; Dipeptides1966-06
45 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
46 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
47 Capecchi, Mario R.Introduction: the molecular genetic analysis of mouse developmentThis paper is an introduction of seven different papers presented in "Seminars in developmental biology" on Molecular Genetic Analysis of Mouse Development . The first paper, by Janet Rossant, describes very early mouse development. The second paper, by Frank Conlon and Rosa Beddington provide an i...Embryo Culture Techniques; Genes1995-04
48 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
49 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
50 KUTV news featurette on cloning, molecular genetics, and disease aired November 9, 1997This 3 minutes, 1 second video clip from Salt Lake City's KUTV, Channel 2 features a short interview with Mario Capecchi concerning cloning and its use in molecular genetics and the study of human diseases.Gene targeting; Genetic engineering; Molecular genetics; Cancer Research; Capecchi, Mario R.; Science - Moral and ethical aspects; Human chromosome abnormalities - Diagnosis; Television feature stories1997-11-09
51 Capecchi, Mario R.Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient miceWhile nephrologists often observe reduced hematocrit associated with inhibitors of angiotensin-converting enzyme (ACE), the basis for this effect is not well understood. We now report that two strains of ACE knockout mice have a normocytic anemia associated with elevated plasma erythropoietin levels...ACE2000-10-31
52 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
53 Local television news clips for June 14, 1994 featuring Mario CapecchiThis is a compilation of news clips from Salt Lake City's four major commercial television stations (Channels 2, 4, 5, and 13) lasting a total of 2 minutes, 59 seconds. The topic is Capecchi's winning of the General Motors Corporation's Alfred P. Sloan Jr. Prize for Outstanding Basic Science Contrib...Transgenic mice; Gene targeting; Cancer - Research - Awards; Capecchi, Mario R.; Science - Awards - United States; Television broadcasting of news1994-06-14
54 Capecchi, Mario R.Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA.Biochemical transformation of thymidine-kinase-deficient (TK-) mouse L cells is enhanced 20 to 40 fold when microinjected plasmid DNA contains regions of the genomes of Rous sarcoma virus or simian virus 40 in addition to the complete herpes simplex virus tk gene, irrespective of the orientation and...Animals; Base Sequence; Genes, Viral; Plasmids; Thymidine Kinase1983-07-01
55 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
56 Thomas, Kirk R.; Capecchi, Mario R.Maintenance of functional equivalence during paralogous Hox gene evolution.Biological diversity is driven mainly by gene duplication followed by mutation and selection. This divergence in either regulatory or protein-coding sequences can result in quite different biological functions for even closely related genes. This concept is exemplified by the mammalian Hox gene comp...Alleles; Animals; Cervical Vertebrae; Embryo; Genetic Complementation Test; Homeodomain Proteins; Homozygote; Mice2000-02-10
57 Capecchi, Mario R.Male fertility is dependent on dipeptidase activity of testis ACE.Testis angiotensin-converting enzyme (ACE) is an isozyme exclusively expressed by developing sperm. This protein has only a single catalytic domain containing the HEXXH consensus-site motif typical of zinc metallopeptidases. The exact role of testis ACE is unknown, but male mice lacking the protein ...Amino Acid Motifs; Blotting, Western; Catalytic Domain; Comparative Study; Isoenzymes; Protein Structure, Tertiary2005-11-11
58 Capecchi, Mario R.Measurement of suppressor transfer RNA activity.Transfer RNA (tRNA) suppression of nonsense mutations in prokaryotic systems has been widely used to study the structure and function of different prokaryotic genes. Through genetic engineering techniques, it is now possible to introduce suppressor (Su+) tRNA molecules into mammalian cells. A quanti...Animals; Cells, Cultured; Eukaryotic Cells; Genes, Viral; Mice; Orthomyxoviridae; Peptide Chain Termination, Translational; Protein Biosynthesis1983-08-26
59 Capecchi, Mario R.Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions.The Hox genes encode transcription factors which mediate the formation of the mammalian body plan along the anteroposterior and appendicular axes. Paralogous Hox genes within the separate linkage groups are closely related with respect to DNA sequence and expression, suggesting that they could have ...Animals; Atlas; Homozygote; Mice; Models, Genetic1994-07-28
60 Kerber, Richard A.Mitochondrial genomic analysis of late onset alzheimers disease reveals protective haplogroups H6A1A/H6A1B: the Cache County study on memory in agingBackground: Alzheimer's disease (AD) is the most common cause of dementia and AD risk clusters within families. Part of the familial aggregation of AD is accounted for by excess maternal vs. paternal inheritance, a pattern consistent with mitochondrial inheritance. The role of specific mitochondrial...2012-01-01
61 Eichwald, Ernst; Capecchi, Mario R.; Thomas, Kirk R.Mouse model for the delta F508 allele of cystic fibrosisThe most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508 ...Digestive System; Disease Models, Animal; Electrolytes; Mice, Inbred C57BL1995-10
62 Capecchi, Mario R.N-formylmethionyl-sRNA as the initiator of protein synthesis.A bizarre fast about Nterminal groups of bacterial proteins. Instead of a random mixture, that the great majority of N-terminal groups were either methionine or alanine. This finding suggested that methionine and alanine constituted start signals for the initiation of polypeptide chains. Alternative...Electrophoresis; Formates; In Vitro; Methionine1966-01-01
63 National Medals of Science and Technology Awards (2001) Ceremony and Banquet, held June 13, 2002This 51 minutes, 5 seconds video is divided into two parts: the first part is a film introducing the award winners and their achievements; the second is the presentation of the actual awards by George W. Bush, President of the United States. Medal winners were: Mario R. Capecchi for his pioneering...Molecular genetics; Gene targeting; Transgenic mice; Gene expression; Genetic engineering; Capecchi, Mario R.; Science - Awards - United States; Awards presentations2002
64 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
65 Capecchi, Mario R.Paralogous mouse Hox genes, Hoxa9, Hoxb9, and Hoxd9, function together to control development of the mammary gland in response to pregnancy.Although the role of Hox genes in patterning the mammalian body plan has been studied extensively during embryonic and fetal development, relatively little is known concerning Hox gene function in adult animals. Analysis of mice with mutant Hoxa9, Hoxb9, and Hoxd9 genes shows that these paralogous g...Embryonic and Fetal Development; Gene Expression Regulation, Developmental; Genotype; Mice, Knockout1999-01
66 Capecchi, Mario R.Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules.We examined the fate of DNA microinjected into nuclei of cultured mammalian cells. The sequence composition and the physical form of the vector carrying the selectable gene affected the efficiency of DNA-mediated transformation. Introduction of sequences near the simian virus 40 origin of DNA replic...Base Sequence; Cell Line; Genes, Viral; Genetic Vectors; Mice; Microinjections1982-11
67 Hansen, Mark S.; Coffin, Cheryl M.; Capecchi, Mario R.Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin.To investigate the role of the translocation-associated gene Pax3:Fkhr in alveolar rhabdomyosarcomas, we generated a Cre-mediated conditional knock-in of Pax3:Fkhr into the mouse Pax3 locus. Exploring embryonic tumor cell origins, we replaced a Pax3 allele with Pax3:Fkhr throughout its expression do...Neuroprogenitor; Embryogenesis2004-11-01
68 Capecchi, Mario R.Polypeptide chain termination in vitro: isolation of a release factor.The growing polypeptide chain remains bound to the ribosome-messenger RNA complex through the sRNA carrying the last amino acid incorporated into the polypeptide chain.' On completion of the polypeptide chain a mechanism must exist for releasing it from the protein-synthesizing machinery. To date, m...Carbon Isotopes; Phenylalanine; Proteins1967-09-01
69 Capecchi, Mario R.Polypetide chain termination. Purification of the release factors, R1 and R2, from Escherichia coli.We have extensively purified the release factors RI and Rz from Escherichia coli. These proteins can each mediate polypeptide chain termination. The physiological substrate for this reaction is a completed polypeptide chain in a peptidyl- transfer RNA-messenger RNA-ribosome complex. The reaction con...Acrylates; Detergents1971-02-25
70 Gussin, Gary N.; Capecchi, Mario R.Protein synthesis directed by DNA phage messengers.Even through the amino acids corresponding to most of the 64 nucleotide triplets are now known, several important aspects of the genetic code are not yet fully understood. In particular we need more knowledge about the "punctuation marks" of the code-for example, the signals necessary for the initia...Carbon Isotopes; Escherichia coli; Genetic Code; Methionine1967-09-01
71 Capecchi, Mario R.Purification and characterization of mouse hypoxanthine-guanine phosphoribosyltransferase.Hypoxanthine-guanine phosphoribosyltransferase (HGPR transferase) (EC 2.4.2.8) has been purified approximately 4500-fold to apparent homogeneity from mouse liver. The procedure involves the use of affinity chromatography and was designed to be readily adaptable to small scale isolations. The enzyme ...Buffers; Centrifugation, Density Gradient; Chromatography, Affinity; Chromatography, Gel; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel1975-01-31
72 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
73 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
74 Capecchi, Mario R.Removing the vertebrate-specific TBP N terminus disrupts placental beta2m-dependent interactions with the maternal immune systemMammalian TBP consists of a 180 amino acid core that is common to all eukaryotes, fused to a vertebrate-specific N-terminal domain. We generated mice having a modified tbp allele, tbp(DeltaN), that produces a version of TBP lacking 111 of the 135 vertebrate-specific amino acids. Most tbp(DeltaN/Delt...Alleles; Animals, Genetically Modified; Binding Sites; Embryonic and Fetal Development; Evolution, Molecular; Female; Fetus; Immune Tolerance; Male; Mice; Mutation; ATA-Box Binding Protein2002-07-12
75 Capecchi, Mario R.Role of Hox genes in mediating the mammalian body planThis is a 1 hour, 5 minutes, 28 seconds video of a lecture given by Mario Capecchi on the genetic analysis of the Hox complex, or Hox cluster and their role in embryogenesis. Using examples such as the development of the hindbrain (rhombencephalon), facial nerves, and hands Capecchi outlines the re...Transgenic mice; Gene targeting; Genetic engineering; Molecular genetics; Homeobox genes; Histology - Pathological; Gene expression; Gene regulation; Genotype; Phenotype
76 Moon, Ann M.; Capecchi, Mario R.Roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth.Although numerous molecules required for limb bud formation have recently been identified, the molecular pathways that initiate this process and ensure that limb formation occurs at specific axial positions have yet to be fully elucidated. Based on experiments in the chick, Fgf8 expression in the in...Animals; Apoptosis; Forelimb; Gene Expression Regulation, Developmental; High Mobility Group Proteins; Hindlimb; In Situ Hybridization; Mesoderm; Mice, Mutant Strains; Trans-Activators2004-09
77 Secret of life module: on the brink, four profiles in groundbreaking scienceThis is a 15 minutes, 12 seconds segment of the WGBH series, Secret of life. Profiles include Dennis Slamon of UCLA and his work on the oncagenes and the creation of excess receptors that play a significant role in breast cancer; Patricia Steeg of the National Cancer Institute (NCI) and her work on...Transgenic mice; Gene targeting; Genetic engineering; Molecular genetics; Cancer - Research; Capecchi, Mario R.; Science - Moral and ethical aspects; Human chromosome abnormalities - Diagnosis; Gene expression; Gene regulation
78 Capecchi, Mario R.Selective degradation of abnormal proteins in mammalian tissue culture cells.The degradation rates of several missense mutants of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) in mouse L cells are compared to those of the wild-type enzyme. Although the rates of total protein breakdown in the mutant cell lines are identical to that of the parental L cell line, ...Gene Expression Regulation; Mice, Transgenic; Microscopy, Fluorescence1974-12-01
79 Capecchi, Mario R.Synthesis of an ochre suppressor tRNA gene and expression in mammalian cells.We have used site-specific mutagenesis to change the anticodon of a Xenopus laevis tyrosine tRNA gene so that it would recognize ochre codons. This tRNA gene is expressed when amplified in monkey cells as part of a SV40 recombinant and efficiently suppresses termination at both the ochre codon separ...Xenopus; Nucleic Acid Conformation; Kidney; DNA Restriction Enzymes1984-11
80 Capecchi, Mario R.Targeted disruption of the even-skipped gene, evx1, causes early postimplantation lethality of the mouse conceptus.Implantation within the mammalian uterus elicits dramatic changes in the growth, differentiation, and morphogenesis of the conceptus. This process is interrupted in mice carrying a targeted disruption of the murine evx1 gene, a homolog of the Drosophila even-skipped (eve) gene. Upon implantation, pr...Extraembryonic; Homozygotes; Drosophila1994-08-15
81 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
82 Capecchi, Mario R.Targeted mutations in hoxa-9 and hoxb-9 reveal synergistic interactions.Mice were generated with a targeted disruption of the homeobox-containing gene hoxb-9. Mice homozygous for this mutation show defects in the development of the first and second ribs. In most cases the first and second ribs are fused near the point at which the first and second pairs of ribs normally...Embryonic and Fetal Development; In Situ Hybridization; Mice, Knockout1997-01-15
83 Capecchi, Mario R.; Bernstein, Kenneth E.; Thomas, Kirk R.Targeting genes for self-excision in the germ lineA procedure is described that directs the self-induced deletion of DNA sequences as they pass through the male germ line of mice. The testes-specific promoter from the angiotensin-converting enzyme gene was used to drive expression of the Cre-recombinase gene. Cre was linked to the selectable marker...Cre-recombinase; Hoxa3; Chimeric mice1999-06-15
84 Hansen, Mark S.; Healy, Lindsey J.; Johnson, Christopher R.; Capecchi, Mario R.; Keller, Charles; Jones, Greg M.Virtual histology of transgenic mouse embryos for high-throughput phenotyping.A bold new effort to disrupt every gene in the mouse genome necessitates systematic, interdisciplinary approaches to analyzing patterning defects in the mouse embryo. We present a novel, rapid, and inexpensive method for obtaining high-resolution virtual histology for phenotypic assessment of mouse ...Forkhead Transcription Factors; Paired Box Transcription Factors2006
85 Capecchi, Mario R.Xanthine oxidoreductase is central to the evolution and function of the innate immune system.The housekeeping enzyme xanthine oxidoreductase (XOR) has been studied intensively over the past 100 years, yet the complexity of its in vivo function is still poorly understood. A large body of literature focuses on the different catalyltic forms of XOR and their importance in the synthesis of reac...Animals; Gene Expression Regulation, Enzymologic; Humans; Immune System; Models, Biological2003-09-01
86 Capecchi, Mario R.Yeast super-suppressors are altered tRNAs capable of translating a nonsense codon in vitro.tRNA isolated from two different yeast super-suppressor strains translates a known nonsense mutation in vitro, whereas tRNA from a closely related nonsuppressing strain does not. Suppression was assayed by translation of RNA isolated from an amber coat mutant of bacteriophage Qbeta (GB11) in a prote...Codon; Escherichia coli; Protein Biosynthesis1975-11
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