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1 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
2 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
3 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
4 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
5 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
6 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
7 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
8 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
9 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
10 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
11 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
12 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
13 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
14 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
15 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
16 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
17 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
18 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
19 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
20 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
21 Newman, LexUnmasking Descartes's case for the bete machine doctrineAmong the more notorious of Cartesian doctrines is the bete machine doctrine -- the view that brute animals lack not only reason, but any form of consciousness (having no mind or soul). Recent English commentaries have served to obscure, rather than to clarify, the historical Descartes's views, Stan...Animals; Intelligence; Soul; Mechanical causation2001
22 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
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