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