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51 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
52 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
53 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
54 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
55 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
56 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
57 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
58 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
59 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
60 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
61 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
62 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
63 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
64 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
65 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
66 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
67 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
68 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
69 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
70 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
71 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
72 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
73 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
74 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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