Mario Capecchi
Distinguished Professor of Biology and Human Genetics
Mario Capecchi
Distinguished Professor of Biology and Human
Genetics
Department of Biology
University of Utah
Dr. Capecchi is professor of Human Genetics and Adjunct professor of Cellular, Viral, and Molecular Biology at the University of Utah School of Medicine and Professor of Biology at the University of Utah. He received his Ph.D. in biology from Harvard University, where he worked with James Watson. Dr. Capecchi remained at Harvard as a Junior fellow of the Society of Fellows and then joined the Harvard faculty before moving to the University of Utah. He is a member of the National Academy of Sciences. Dr. Capecchi's honors include the Bristol-Myers Squibb Award for distinguished achievement in neuroscience research, the Gairdner Foundation International Award, and the General Motors Corporation's Alfred P. Sloan Jr. Prize.
With his success in breeding mice that have specific targeted genes inactivated ("knock-out" mice), Dr. Mario Renato Capecchi established a new method for exploring how genes work. His methods of "gene targetting," which make it possible to substitute a gene with desired mutations for any gene in the cells of higher animals, have enabled medicine and biology to freely generate and study cells with genetic mutations of special interest. It was for this work that he received the 1996 Kyoto Prize in basic sciences.
The practical applications of "knock-out" mice have opened broad new areas of research in embryology and helped elucidate the genetic functions of vertebrate animals in such areas as the study of receptor functions, signal transmission cellular formation analysis. Presently, in the field of medical research, those techniques are actively used to produce disease-model animals in order to investigate the molecular pathology of hereditary disease and develop genetic therapy techniques.
Current Research:
Mammalian development, gene targeting, embryo-derived stem cells, Hox genes and cell-cell signaling
Homologous recombination between DNA sequences residing in the chromosome and newly introduced DNA sequences, termed gene targeting, provides the means for specifically modifying any gene in any desired manner in cultured mammalian cells. If the recipient cell for the gene modification is a pluripotent, mouse embryo-derived stem cell, then the means are available for creating chimeric mice from these cells that will transfer the altered gene to their progeny. With this technology, the biological function of any cloned gene can be determined in the living mouse.
We are using this technology to genetically dissect early development in the mouse. Our efforts are directed towards determining the function of two sets of genes in development. The first set is involved in localized developmental decision through cell-cell signaling. The second set includes members of a transcriptional developmental program that specify positional value in the early mouse embryo.
Capecchi, M.R. (1989). The new mouse genetics: altering the genome by gene targeting. Trends in Genetics 5:70-76.
Capecchi, M.R. (1989). Altering the genome by homologous recombination. Science 244:1288-1292.
Thomas, K.R., and M.R. Capecchi. (1990). Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346: 847-850.
Chisaka, O. and M.R. Capecchi. (1991). Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 350:473-479.
Chisaka, O., T.S. Musci, and M.R. Capecchi. (1992). Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene hox-1.6. Nature 355:516-520.
Mansour, S. L., J. M. Goddard and M. R. Capecchi (1993). Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear. Development 117:13-28.
Carpenter, E. M., J. M. Goddard, O. Chisaka, N. R. Manley and M. R. Capecchi (1993). Loss of Hoxa-1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development 118:1063-1075.
Condie, B. G. and M. R. Capecchi (1993). Mice homozygous for a targeted disruption of Hoxd-3 (Hox-4.1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis. Development 119:579-595.
Capecchi, M. R. (1994). Targeted gene replacement. Sci. Am. 270:54-61.
Davis, A. P. and M. R. Capecchi (1994). Axial homeosis and appendicular skeleton defects in mice with targeted disruption of hoxd-11. Development 120:2187-2198.
Condie, B. G. and M. R. Capecchi (1994). Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Nature 370:304-307.