MARIO R. CAPECCHI
Mario Capecchi
e-mail: mario.capecchi@genetics.utah.edu		 Distinguished Professor of Biology and Human Genetics
Investigator of the Howard Hughes Institute
Co-Chair of Human Genetics

Capecchi lab
Developmental Neuroscience

B.S. 1961, Antioch College; Ph.D. 1967, Harvard University.

RESEARCH:

Gene manipulation in mammalian and other eukaryotic cells

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 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.

Dr. Capecchi is using this technology to genetically dissect neurogenesis and behavior in the mouse.

Selected Publications

Tvrdik, P., and Capecchi, M.R. (2006) Reversal of Hox1 gene subfunctionalization in the mouse. Dev Cell., Aug;11(2):239-250.

Wu, S., Wu, Y., and Capecchi, M. R. (2006) Motoneurons and oligodendrocytes are sequentially generated from neural stem cells but do not appear to share common lineage-restricted progenitors in vivo. Development, 133:581-590.

Vorbach, C., Capecchi, M. R., and Penninger, J. M. (2006) Evolution of the mammary gland from the innate immune system? Bioessays, Jun;28(6):606-616.

Keller, C. B., and Capecchi, M. R. (2005) New Genetic Tactics to Model Alveolar Rhabdomyosarcoma in the Mouse. Cancer Res., Sept. 1; 65(17):7530-7532.

Kindlmann G. L., Weinstein, D. M., Jones, G. M., Johnson, C. R., Capecchi, M. R., and Keller, C. (2005) Practical vessel imaging by computed tomography in live transgenic mouse models for human tumors. Molecular Imaging, Oct-Dec;4(4):417-424.

Xiao, H. D., Fuchs, S., Campbell, D. J., Lewis, W., Dudley, S. C., Jr., Kasi, V. S., Hoit, B. D., Keshelava, G. T., Zhao, H., Capecchi, M. R., and Bernstein, K. E. (2004) Mice with cardiac restricted angiotensin converting enzyme (ACE) have atrial enlargement and sudden death. Am. J. Path., 165:1019-1032.

Keller, C., Hansen, M. S., Coffin, C. M., and Capecchi, M. R. (2004) Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Genes Dev., 18:2608-2613.

Keller, C., Arenkiel, B. R., Coffin, C. M., El-Bardeesy, N., DePinho, R. A., and Capecchi, M. R. (2004) Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function. Genes Dev. 18:2614-2626.

Boulet, A. M., Moon, A. M., Arenkiel, B. R., and Capecchi, M. R. (2004) The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth. Dev. Biol., 273:361-372.

Arenkiel, B. R., Tvrdik, P., Gaufo, G. O., and Capecchi, M. R. (2004) Hoxb1 functions in both motoneurons and tissues of the periphery to establish and maintain the proper neuronal circuitry. Genes Dev., 18:1539-1552.

Gaufo, G. O., Wu, S., and Capecchi, M. R. (2004) Contribution of Hox genes to the diversity of the hindbrain sensory system. Development, 131:1259-1266.

Gaufo, G. O., Thomas, K. R., and Capecchi, M. R. (2003) Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motor neurons. Development, 130:5191-5201.

Wellik, D. M., and Capecchi, M. R. (2003) Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science, 301:363-367.

Arenkiel, B. R., Gaufo, G. O., and Capecchi, M. R. (2003) Hoxb1 neural crest preferentially form glia of the PNS. Dev. Dynamics, 227:379-386.

Wellik, D. M., Hawkes, P. J., and Capecchi, M. R. (2002) Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev., 16:1423-1432.

Vorbach, C., Scriven, A., and Capecchi, M. R. (2002) The housekeeping gene Xanine Oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland. Genes Dev., 16:3223-3235.

Hobbs, N. K., Bondareva, A. A., Barnett, S., Capecchi, M. R., and Schmidt, E. E. (2002) Removing the vertebrate-specific TBP N-terminus disrupts placental b2m-dependent interactions with the maternal immune system. Cell, 110:43-54.

Greer, J. M., and Capecchi, M. R. (2002) Hoxb8 is required for normal grooming behavior in the mouse. Neuron 33:23-34.

Capecchi, M. R. (2001) Generating mice with targeted mutations. Nature Med., 7:1086-1090.

Moon, A. M., and Capecchi, M. R. (2000) Fgf8 is required for outgrowth and patterning of the limbs. Nature Genet. 26:455-459.

Gaufo, G. O., Flodby, P., and Capecchi, M. R. (2000) Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development127:5343-5354.

Schmidt, E. E., Taylor, D. S., Prigge, J. R., Barnett, S., and Capecchi, M. R. (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc. Natl. Acad. Sci. USA 97:13702-13707.

Barrow, J. R., Stadler, H. S., and Capecchi, M. R. (2000) Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127:933-944.

Greer, J. M., Puetz, J., Thomas, K. R., and Capecchi, M. R. (2000) Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 403:661-665.

Rossel, M., and Capecchi, M. R. (1999) Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development 126:5027-5040.

Capecchi, M. R. (1997) The role of Hox genes in hindbrain development. In: Molecular and Cellular Approaches to Neural Development. (W.M. Cowan, T.M. Jessell and S.L. Zipursky, Eds.) New York: Oxford University Press. pp. 334-355.

Goddard, J. M., Rossel, M., Manley, N. R., and Capecchi, M. R. (1996) Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 122:3217-3228.

Davis, A. P., Witte, D. P., Hsieh-Li, H. M., Potter, S. S., and Capecchi, M. R. (1995) Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature 375:791-796.

Condie, B. G., and Capecchi, M. R. (1994) Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Nature 370:304-307.

Capecchi, M. R. (1994) Targeted gene replacement. Sci. Am. 270:54-61.

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