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26 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
27 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
28 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
29 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
30 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
31 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
32 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
33 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
34 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
35 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
36 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
37 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
38 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
39 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
40 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
41 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
42 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
43 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
44 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
45 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
46 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
47 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
48 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
49 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
50 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
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