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1 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
2 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
3 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
4 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
5 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
6 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
7 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
8 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
9 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
10 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
11 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
12 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
13 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
14 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
15 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
16 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
17 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
18 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
19 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
20 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
21 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
22 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
23 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
24 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
25 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
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