capecchi

Since nearly all biological phenomena are mediated by genes, gene targeting is impacting the analysis of nearly all aspects of mammalian biology, including studies in evolution, development, neurobiology, immunology and human disease. This technology has many applications for clinical medicine. Scientists can simulate any human genetic disease in laboratory models, study its progression, and test potential therapies against it. In the future, since the investigator can choose which gene to modify and precisely how to modify it, therapies based on gene targeting will be used to correct the endogenous defective gene in the appropriate human tissue. These therapies will be directed at the cause rather than at the symptoms of the disease.

An immediate application of gene targeting to human medicine is to generate animal models for human disease such as diabetes, atherosclerosis, hypertension and cancer. These models provide a unique opportunity to undertake in-depth analysis of the pathology of human diseases, and they offer a platform for developing new therapeutic protocols.

Lab Website (link)

Our research efforts are directed towards the analysis of the developmental programs mediating pattern formation, organogenesis and neurogenesis in the mouse. Towards achieving these goals, we have pioneered the technology required for generating mutations in any gene in the mouse. This technology employs the exchange of DNA sequences, by homologous recombination, between exogenous, newly added DNA sequences and the cognate chromosomal DNA sequences in embryo-derived mouse stem (ES) cells. This process is referred to as “gene-targeting”. The ES cells containing the desired targeting event are then used to generate mouse germ line chimeras, capable of transmitting the mutation to their progeny. We are using this technology to determine the function of genes believed to mediate important developmental decisions in the mouse embryo. This technology is also being used to generate mouse models for human genetic diseases. Such animals allow a deeper analysis of the pathogenesis of the human disease, as well as provide appropriate subjects for testing new therapeutic protocols including somatic gene therapy.

Rollins, M.F., D. van der Heide, C. Weisend, J. Kundert, K. Constock, E. Sovorova, M.R. Capecchi, G.F. Merrill and E.E. Schimdt (2010). Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration. Cell Sci. (in press).

Chen S.C., P. Tvrdik, E. Peden, S. Cho, S. Wu, G. Spangrude, M.R. Capecchi (2010). Hematopoietic Origin of Pathological Grooming in Hoxb8 Mutant Mice. Cell 141(5):775-785. PMID20510925

Makki, N. and M. R. Capecchi (2010). Hoxa1 linage-tracing indictes a direct role for Hoxa1 in development of the inner ear, the heart and the third rhombomere. Dev Bio.341:499–509. PMID20171203

Tripathi, P., Q. Guo, Y. Wang, M. Coussens, H. Liapis, S. Jain, M. R. Kuehn, M. R. Capecchi and F. Chen (2010). Midline signaling regulates kidney positioning but not nephrogenesis through Shh. Dev Bio. Epub Feb10. PMID 20152829

Jones, K. B., V. Piombo, C. Searby, G. Kurringer, B. Yang, F. Grabellus, P. Roughley, J. Morcuende, J. Buckwalter, M. R. Capecchi, A. Vortkamp and V. C. Sheffield (2010). A mouse model of osteochondromagenesis from clonal inactivation of Ext1 in chondroytes. PNAS 107(5):2054-9. Epub 2009 Dec 22. PMID20080592

Suvorova, E., O. Lucas, M.C. Weisend, M.F. Rollins, G. Merrill, M.R. Capecchi, and E. Schmidt. (2009) Cytoprotective Nrf2 Pathway Is Induced In Chronically Txnrd1-Deficient Hepatocytes. PLoS ONE Jul 7:4(7):e6158. PMID 19584930

Xue, H., S. Wu, S.T. Papadeau, S. Spusta, A.M. Swistowska, C.C. MacArthur, M.P. Mattson, N. J. Maragakis, M.R. Capecchi, M.S. Rao, S. Zeng and Y. Liu. (2009) A targeted neuroglial reporter line generated by homologous recombination in human embryonic stem cells. Stem Cell 27(8): 1836-46 PMID19544414

Haldar, M., M. Hedberg, M. Hockin and M.R. Capecchi (2009). A CreER based random induction strategy for modeling translocation-associated sarcomas in mice. Cancer Res.15:69(8):3657-64. PMID19351831

Sangiorgi, E. and M.R. Capecchi (2009). Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis. PNAS Apr:106(17):7101-7106. PMID19372370

Ootani, A., X. Li, E. Sangiorgi, Q.T. Ho, H. Ueno, S. Toda, H. Sugihara, K. Fujimoto, I.L. Weissman, M.R. Capecchi and C.J. Kuo (2009). Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat. Med. 5(6): 701-6 Epub Apr 27. PMID19398967

Nishijo, K., T. Hosoyama, C.R.R. Bjornson, B.S. Schaffer, S.I. Prajapati, A.N. Bahadur, M.S. Hansen, M.C. Blandford, A.T. McCleish, B.P. Rubin, J.A.Epstein, T.A. Rando, M.R. Capecchi and C. Keller (2009). Biomarker system for studying muscle, stem cells, and cancer in vivo. FASEB 23(8): 2681-90 Epub Mar 30. PMID19332644

Taniguchi, E., M.J. Cho, B.R. Arenkiel, M.S. Hansen, O.J. Rivera, A.T. McCleish, S.J. Qualman, D.C. Guttridge, M.P. Scott, M.R. Capecchi and C. Keller (2009). Bortezomib reverses a post-translational mechanism of tumorigenesis for patched 1 haploisufficiency in medulloblastoma. Pediatr. Blood Cancer53(2) 136-44. PMID19213072

Ying, G., S. Wu, R. Hou, W. Huang, M.R. Capecchi, Q. Wu (2009). The protocadherin gene Celsr3 is required for interneuron migration in the mouse forebrain. Mol. Cell. Biol. 29(11): 3056-61 Epub Mar 30. PMID 19332558

Ray, R., and M.R. Capecchi (2008). An examination of the chiropteran HoxD locus from an evolutionary perspective. Evol. & Dev.10(6):657-670. PMID19021736

Jia Q., B.W. McDill, B. Sankarapandian, S. Wu, H. Liapis, L.B. Holzman, M.R. Capecchi, J. H. Miner, F. Chen (2008). Ablation of developing podocytes disrupts cellular interactions and nephrogenesis both inside and outside the glomerulus. Am. J. Physiol. Renal Physiol.295(6): F1790-8 Epub 2008 Oct 8. PMID18842818

Sangiorgi, E., Z. Shuhua, and M.R. Capecchi (2008). In vivo evaluation of PhiC31 recombinase activity using a self-excision cassette. Nuc. Acid Res. Nov;36(20):e134. Epub 2008 Oct 1. PMID18829714

Kundert, J.A., A.L. Sealey, Y. Li, M.R. Capecchi and E.E. Schmidt (2008). Syngeneic immune-dependent abortions in mice suggest paternal alloantigen-independent mechanisms. Am. J. Reprod. Immunol.60(4): 290-7. PMID18759828

Capecchi, M.R. (2008). The Making of a Scientist II (Nobel Lecture). ChemBioChem. Jul 2;9(10):1530-43. Epub Jun 13. PMID18551693

Sangiorgi, E. and M.R. Capecchi (2008). Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. Jul;40(7):915-20. PMID18536716

Haldar, M., R.L. Randall and M. R. Capecchi (2008). Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling. Clin OrthopRelat Res. Sep;466(9):2156-67. PMID18563504

Haldar, M. G. Karan, P. Tvrdik, and M.R. Capecchi (2008). Two cell lineages, Myf5-independent, participate in mouse skeletal myogenesis. Dev Cell Mar(3)14:437-445. PMID18331721

Wu, S., G. Ying, Q. Wu and M.R. Capecchi (2008). A protocol for constructing gene targeting vectors: generating knockout mice for the cadherin family and beyond. Nat Protocols. 3(6):1056-76. PMID18546598

Vasquez, S.X., M.S. Hansen, A.N. Bahadur, M.F. Hockin, G.L. Kindlmann, L. Nevell, I.Q. Wu, D.J. Grunwald, D.M. Weinstein, G.M. Jones, C.R. Johnson, J.L. Vandeberg, M.R. Capecchi, C. Keller (2008). Optimization of volumetric computed tomography for skeletal analysis of model genetic organisms. Anat Rec 291(5):475-487. PMID18286615

Wu, Y., G. Wang, S.A. Scott, and M.R. Capecchi (2008). Hoxc10 and Hoxd10 regulate mouse columnar, divisional, and motor pool identity of lumbar motoneurons. Development 135(1):171-182. PMID18065432

Bondareva, A.A., M.R. Capecchi, S.V. Iverson, Y. Li, N.I. Lopez, O. Lucas, G.F. Merrill, J.R. Prigge, A.M. Siders, M. Wakamiya, S.L. Wallin, and E.E. Schmid (2007). Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome. Free Radic Biol Med. Sept. 15;43(6):911-23. PMID17697936

Barrow, J.R., W.D. Howell, M. Rule, S. Hayashi, K.R. Thomas, M.R. Capecchi, and A.P. McMahon (2007). Wnt3 signaling in the epiblast is required for proper orientation of the anteroposterior axis. Dev. Biol. 312:312-20. PMID18028899

McIntyre, D.C., S. Rakshit, A.R. Yallowitz, L. Loken, L. Jeannotte, M.R. Capecchi, and D.M. Wellik (2007). Hox patterning of the vertebrate rib cage. Development134:2981-89. PMID17626057

Wu, S., G. Ying, Q. Wu, and M.R. Capecchi (2007). Towards simpler and faster genome-wide mutagenesis in mice. Nat Genet. Jul;39(7):922-30. PMID1757267

Shen, X.Z., P. Li, D. Weiss, S. Fuchs, H.D. Xiao, J.A. Adams, I.R. Williams, M.R. Capecchi, W.R. Taylor, and K.E. Bernstein (2007). Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma. Am J Pathol. Jun;170(6):2122-34. PMID17525278

Haldar, M., J.D. Hancock, C.M. Coffin, S.L. Lessnick, and M.R. Capecchi (2007). A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer Cell. Apr.;11(4):375-388. PMID17418413

Tvrdik, P. and M.R. Capecchi (2006). Reversal of Hox1 gene subfunctionalization in the mouse. Dev Cell. Aug;11(2):239-50. PMID16890163

Frenzel, K., T.A. Wallace, I. McDoom, H.D. Xiao, M.R. Capecchi, K.E. Bernstein, and P.P. Sayeski (2006). A functional Jak2 tyrosine kinase domain is essential for mouse development. Exp Cell Res. Sept. 10;312(15):2735-44. PMID16887119

Vorbach, C., M.R. Capecchi, and J.M. Penninger (2006). Evolution of the mammary gland from the innate immune system? Bioessays. Jun;28(6):606-16. PMID16700061

Westerberg, R., J.E. Mansson, V. Golozoubova, I.G. Shabalina, E.C. Backlund, P. Tvrdik, K. Retterstol, M.R. Capecchi, and A. Jacobsson (2006). ELOVL3 is an important component for early onset of lipid recruitment in brown adipose tissue. J Biol Chem. Feb. 24;281(8):4958-68. PMID16326704

Johnson, J.T., M.S. Hansen, I. Wu, L.J. Healy, C.R. Johnson, G.M. Jones, M.R. Capecchi, and C. Keller (2006). Virtual histology of transgenic mouse embryos for high-throughput phenotyping. PLoS. Apr;2(4):e61. PMID16683035

Wu, S., Y. Wu, and M.R. Capecchi (2006). Motoneurons and oligodendrocytes are sequentially generated from neural stem cells but do not appear to share common lineage-restricted progenitors in vivo. Development133:581-590. PMID16407399

Fuchs, S., K. Frenzel K., C. Hubert, R. Lyng, L. Muller, A. Michaud, H.D. Xiao, J.W. Adams, M.R. Capecchi, P. Corvol, B.D. Shur, and K.E. Bernstein (2005). Male fertility is dependent on dipeptidase activity of testis ACE. Nat Med. Nov;11(11):1140-2. PMID16270063

Kindlmann G.L., D.M. Weinstein, G.M. Jones, C.R. Johnson, M.R. Capecchi, and C. Keller. (2005) Practical vessel imaging by computed tomography in live transgenic mouse models for human tumors. Molecular Imaging. Oct-Dec;4(4):417-24. PMID16285903

Keller, C.B. and M.R. Capecchi. (2005) New Genetic Tactics to Model Alveolar Rhabdomyosarcoma in the Mouse. Cancer Res. Sept. 1; 65(17):7530-32. PMID16140913

Schindehutte J, H. Fukumitsu, P. Collombat, G. Griesel, C. Brink, P.C. Baier, M.R. Capecchi, and A. Mansouri (2005). In vivo and in vitro tissue-specific expression of green fluorescent protein using the cre-lox system in mouse embryonic stem cells. Stem Cells, 23(1), 10-15. PMID15625119

Capecchi, M.R. (2005). Essay: Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet. 2005 Jun;6(6):507-12. PMID15931173

Keller, C., B. R. Arenkiel, C. M. Coffin, N. El-Bardeesy, R. A. DePinho and M. R. Capecchi (2004). Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function. Genes Dev.18:2614-2626. PMID15489287

Austin, C.P., J.F. Battey, A. Bradley, M. Bucan, M.R. Capecchi, F.S. Collins, W.F. Dove, G. Duyk, S. Dymecki, J.T. Eppig, F.B. Grieder, N. Heintz, G. Hicks, T.R. Insel, A. Joyner, B.H. Koller, K.C. Lloyd, T. Magnuson, M.W. Moore, A. Nagy, J.D. Pollock, A.D. Roses, A.T. Sands, B. Seed, W.C. Skarnes, J. Snoddy, P. Soriano, D.J. Stewart, F. Stewart, B. Stillman, H. Varmus, L. Varticovski, I.M. Verma, T.F. Vogt, H. von Melchner, J. Witkowski, R.P. Woychik, W. Wurst, G.D. Yancopoulos, S.G. Young and B. Zambrowicz (2004). The knockout mouse project. Nat Genet.36(9): 921-4. PMID 15340423

Keller, C., M. S. Hansen, C. M. Coffin and M. R. Capecchi (2004). Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Genes Dev. 18:2608-2613. PMID15520281

Xiao, H. D., S. Fuchs, D. J. Campbell , W. Lewis, S. C. Dudley, Jr., V. S. Kasi, B. D. Hoit, G. T. Keshelava , H. Zhao, M. R. Capecchi and K. E. Bernstein (2004). Mice with cardiac restricted angiotensin converting enzyme (ACE) have atrial enlargement and sudden death. Am. J. Path. 165:1019-1032. PMID15331425

Boulet, A. M., A. M. Moon, B. R. Arenkiel and M. R. Capecchi (2004). The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth. Dev. Biol.273:361-372. PMID15328019

Arenkiel, B. R., P. Tvrdik, G. O. Gaufo and M. R. Capecchi (2004). Hoxb1 functions in both motoneurons and tissues of the periphery to establish and maintain the proper neuronal circuitry. Genes Dev.18:1539-1552. PMID15198977

Fuchs, S., H. D. Xiao, J. W. Adams, K. Frenzel, G. Keshelava , M. R. Capecchi , P. Corvol and K. E. Bernstein (2004). Role of the N-terminal catalytic domain of ACE investigated by targeted inactivation in mice. J. Biol. Chem. 279:15946-15953. PMID14757757

Gaufo, G.O., S. Wu and M. R. Capecchi (2004). Contribution of Hox genes to the diversity of the hindbrain sensory system. Development 131:1259-1266. PMID14960494

Westerberg, R., P. Tvrdik, A. B. Unden, J. E. Mansson, L. Norlen, A. Jakobsson, W. H. Holleran, P. M. Elias, A. Asadi, P. Flodby, R. Toftgard, M. R. Capecchi and A. Jacobsson (2004). Role for ELOVL3 and fatty acid chain length in development of hair and skin function. J. Biol. Chem. 279:5621-5629. PMID14581464

Boulet, A. M. and M. R. Capecchi (2004). Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Development131:299-309. PMID14668414

Wong, K. H. H., H. D. Wintch and M. R. Capecchi (2004). Hoxa11 regulates stromal cell death and proliferation during neonatal uterine development. Molec. Endocrin. 18:184-193. PMID14551265

Gaufo, G. O., K. R. Thomas and M. R. Capecchi (2003). Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motor neurons. Development130:5191-5201. PMID12954718

Vorbach, C., R. Harrison and M. R. Capecchi (2003). Xanthine oxidoreductase is central to the evolution and function of the innate immune system. Trends Immunol. 29:512-517. PMID12967676

Wellik, D. M. and M. R. Capecchi (2003). Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science301:363-367. PMID12869760

Arenkiel, B. R., G. O. Gaufo and M. R. Capecchi (2003). Hoxb1 neural crest preferentially form glia of the PNS. Dev. Dynamics227:379-386. PMID12815623

Economides, K. R. and M. R. Capecchi (2003). Hoxb13 is required for normal differentiation and secretory function of the ventral prostate. Development130:2061-2069. PMID12668621

Cole J., N. Khokhlova, R. L. Sutliff, J. W. Adams, K. M. Disher, H. Zhao, M. R. Capecchi, P. Corvol and K. E. Bernstein (2003). Mice lacking endothelial angiotensin-converting enzyme (ACE): normal blood pressure with elevated angiotensin II. Hypertension41:313-321. PMID12574101

Economides, K. D., L. Zeltser and M. R. Capecchi (2003). Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae. Dev. Biol.256:317-330. PMID 12679105

Schmidt, E. E., A. A. Bondareva, J. R. Radke and M. R. Capecchi (2003). Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein. J. Biol. Chem.278:6168-6174. PMID12471023

Barrow, J. R., K. R Thomas, O. Boussadia-Zahui, R. Moore, R. Kemler, M. R. Capecchi, and A. P. McMahon (2003). Ectodermal Wnt3/b-catenin signaling is required for the establishment and the maintenance of the apical ectodermal ridge. Genes Dev.17:394-409. PMID12569130

Vorbach, C., A. Scriven and M. R. Capecchi (2002). The housekeeping gene Xanthine Oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland. Genes Dev.16:3223-3235. PMID12562743

Frank, D. U., L. K. Fotheringham, J. A. Brewer, L. J. Muglia, M. Tristani-Firouzi, M. R. Capecchi and A. M. Moon (2002). An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome. Development129:4591-4603. PMID12223415

Boulet, A. M. and M. R. Capecchi (2002). Duplication of the Hoxd11gene causes alterations in the axial and appendicular skeleton of the mouse. Dev. Biol.249:96-107. PMID12217321

Hobbs, N. K., A. A. Bondareva, S. Barnett, M. R. Capecchi and E. E. Schmidt (2002). Removing the vertebrate-specific TBP N-terminus disrupts placental b2m-dependent interactions with the maternal immune system. Cell110:43-54. PMID12150996

Wellik, D. M., P. J. Hawkes and M. R. Capecchi (2002). Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev.16:1423-1432. PMID12050119

Greer, J. M. and M. R. Capecchi (2002). Hoxb8 is required for normal grooming behavior in the mouse. Neuron 33:23-34. PMID11779477

Cole, J., D. L. Quach, K. Sundaram, P. Corvol, M. R. Capecchi and K. E. Bernstein (2002). Mice lacking endothelial ACE have a normal blood pressure. Circ. Res. 90:87-92. PMID 11786523

Capecchi, M.R. (2001). Generating mice with targeted mutations. Nature Med. 7:1086-1090. PMID11590420

Capecchi, M.R. (2001). Gene targeting: Altering the genome in mice. Ergito. http://www.ergito.com/main.jsp?bcs=EXP.3.4

Stadler, H. S., K. M. Higgins and M. R. Capecchi (2001). Loss of Eph-receptor expression correlates with loss of cell adhesion and chondrogenic capacity in Hoxa13mutant limbs. Development 128:4177-4188. PMID11684655

Manley, N. R., J. R. Barrow, T. Zhang and M. R. Capecchi (2001). Hoxb2 and Hoxb4 act together to specify ventral body wall formation. Dev. Biol.237:130-144. PMID11518511

Cole, J., D. Ertoy, H. Lin, R. L. Sutliff, E. Ezan, T. T. Guyene, M. R. Capecchi, P. Corvol, and K. E. Bernstein (2000). Lack of angiotensin II-facilitated erythropoisis causes anemia in angiotensin-converting enzyme-deficient mice. J. Clin. Invest.106:1391-1398. PMID 11104792

Moon, A. M. and M. R. Capecchi (2000). Fgf8 is required for outgrowth and patterning of the limbs. Nat. Genet.26:455-459. PMID11101845

Gaufo, G. O., P. Flodby and M. R. Capecchi (2000). Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development 127:5343-5354. PMID11076756

Schmidt, E. E., D. S. Taylor, J. R. Prigge, S. Barnett and M. R. Capecchi (2000). Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc. Natl. Acad. Sci. USA 97:13702-13707. PMID11087830

Capecchi, M. R. (2000). Choose your target. Nat. Genet.26:159-161. PMID11017070

Capecchi, M. R. (2000). How close are we to implementing gene targeting in animals other than the mouse? Proc. Natl. Acad. Sci. USA 97:956-957. PMID10655465

Moon, A. M., A. M. Boulet and M. R. Capecchi (2000). Normal limb development in conditional mutants of Fgf4. Development 127:989-996. PMID10662638

Barrow, J. R., H. S. Stadler and M. R. Capecchi (2000). Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127:933-944. PMID10662633

Greer, J. M., J. Puetz, K. R. Thomas and M. R. Capecchi (2000). Maintenance of functional equivalence during paralogous Hox gene evolution. Nature403:661-665. PMID10688203

Capecchi, M. R. (2000). Human germline gene therapy: How and why. In Engineering the Human Germline. (G. Stock and J. Campbell, Eds.) New York: Oxford University Press, pp. 31-42.

Hashimoto, J., G. Murakami, M. H. Tsugane, O. Chisaka, M. R. Capecchi and T. Ogino (1999). Lumbosacral plexus in Hoxa9 knockout mice with special reference to their nerve variations identified according to whether they were interphenotypic or intergenotypic differences. Kaibogaku Zasshi 74:609-630. PMID10659578

Godwin, A. R. and M. R. Capecchi (1999). Hair defects in Hoxc13 mutant mice. J. Invest. Dermatol. Symp. Proc. 4:244-247. PMID10674376

Rossel, M. and M. R. Capecchi (1999). Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development126:5027-5040. PMID10529420

Barrow, J. R. and M. R. Capecchi (1999). Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants. Development 126:5011-5026. PMID10529419

Bunting, M., K. E. Bernstein, J. M. Greer, M. R. Capecchi and K. R. Thomas (1999). Targeting genes for self-excision in the germline. Genes Dev.13:1524-1528. PMID10385621

Schmidt, E. E., E. S. Hanson and M. R. Capecchi (1999). Sequence-independent assembly of spermatid mRNAs into mRNP particles. Mol. Cell. Biol. 19:3904-3915. PMID10207114

Chen, F. and M. R. Capecchi. (1999). The paralogous mouse Hox genes, Hoxa9, Hoxb9 and Hoxd9, function together to control development of the mammary gland in response to pregnancy. Proc. Natl. Acad. Sci. USA 96:541-546. PMID9892669

Godwin, A. R., H. S. Stadler, K. Nakamura and M. R. Capecchi. (1998). Detection of targeted GFPHox gene fusions during mouse embryogenesis. Proc. Natl. Acad. Sci. USA 95:13042-13047. PMID9789037

Chen, F., J. Greer and M. R. Capecchi (1998). Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of the different sets of vertebrae. Mech. Dev. 77:49-57. PMID9784603

Capecchi, M. R. (1998). Gene targeting: an historical perspective. In Novel Systems for the Study of Human Diseases–From Basic Research to Applications. pp. 49-54. OECD Proceedings.

Manley, N. R. and M. R. Capecchi (1998). Hox group 3 paralogs regulate the development and migration of the thymus, thyroid and parathyroid glands. Dev. Biol. 195:1-15. PMID9520319

Godwin, A. R. and M. R. Capecchi (1998). Hoxc13 mutant mice lack external hair. Genes Dev. 12:11-20. PMID9420327

Hostikka, S. L. and M. R. Capecchi (1998). The mouse Hoxc11 gene: genomic structure and expression pattern. Mech. Dev. 70:133-145. PMID 9510030

Capecchi, M. R. (1997). The Making of a Scientist. In Kyoto Prizes and Inamori Grants 1996. Kyoto: The Inamori Foundation.

Wilder, P. J., D. Kelly, K. Brigman, C. L. Peterson, T. Nowling, Q.-S. Gao, R. D. McComb, M. R. Capecchi and A. Rizzino (1997). Inactivation of the FGF-4 gene in embryonic stem cells alters the growth and/or the survival of their early differentiated progeny. Dev. Biol. 192:614-629. PMID9441693

Manley, N. R. and M. R. Capecchi (1997). Hox group 3 paralogous genes act synergistically in the formation of somitic and neural crest-derived structures. Dev. Biol.192:274-288. PMID9441667

Condie, B. C., G. Bain, D. I. Gottlieb and M. R. Capecchi (1997). Cleft palate in mice with a targeted mutation in the g-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67. Proc. Natl. Acad. Sci. USA94:11451-11455. PMID9326630

Capecchi, M. R. (1997). Hox genes and mammalian development. In Cold Spring Harbor Symposia on Quantitative Biology: Pattern Formation during Development. Vol. LXII. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, pp. 273-281. PMID959861

Carpenter, E. M., J. M. Goddard, A. P. Davis, T. P. Nguyen and M. R. Capecchi (1997). Targeted disruption of Hoxd10 affects mouse hindlimb development. Development 124:4505-4514. PMID9409668

Esther, C. R., Jr., E. M. Marino, T. E. Howard, A. Machaud, P. Corvol, M. R. Capecchi and K. E. Bernstein (1997). The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice. J. Clin. Invest. 99:2375-2385. PMID9153279

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.

Thomas, K. R. and M. R. Capecchi (1997). Recombinant DNA technique and sickle cell anemia research. Science. 275:1404-1405. PMID9072801

Humphries, M. M., D. Rancourt, G. J. Farrar, P. Kenna, M. Hazel, R. A. Bush, P. A. Sieving, D. M. Sheils, N. McNally, P. Creighton, A. Erven, A. Boros, K. Gulya, M. R. Capecchi and P. Humphries (1997). Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nature Genet.15:216-219. PMID9020854

Chen, F. and M. R. Capecchi (1997). Targeted mutations in Hoxa-9 and Hoxb-9 reveal synergistic interactions. Dev. Biol. 181:186-196. PMID9013929

Capecchi, M. R. (1996). Function of homeobox genes in skeletal development. In Molecular and Developmental Biology of Cartilage, Vol. 785. (B. de Crombrugghe, W. A. Horton, B. R. Olsen, and F. Ramirez, Eds.) Ann. N. Y. Acad. Sci. 785:34-37. PMID8702174

Esther, C. R., Jr., T. E. Howard, Y. Zhou, M. R. Capecchi, M. B. Marrero and K. E. Bernstein (1996). Lessons from angiotensin-converting enzyme-deficient mice. Curr. Opin. Nephrol. Hypertens. 5:463-467. PMID8978990

Barrow, J. R. and M. R. Capecchi (1996). Targeted disruption of the hoxb-2 locus in mice interferes with expression of hoxb-1 and hoxb-4. Development122:3817-3828. PMID9012503

Goddard, J. M., M. Rossel, N. R. Manley and M. R. Capecchi (1996). Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 122:3217-3228. PMID8898234

Esther, C. R., Jr., T. E. Howard, E. M. Marino, J. M. Goddard, M. R. Capecchi and K. E. Bernstein (1996). Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab. Invest. 74:953-965. PMID8642790

Boulet, A.M. and M.R. Capecchi (1996). Targeted disruption of hoxc-4 causes esophageal defects and vertebral transformations. Dev. Biol. 177:232-249. PMID8660891

Delort, J.P. and M.R. Capecchi (1996). TAXI/UAS: a molecular switch to control expression of genes in vivo. Hum. Gene Ther. 7:809-820. PMID8860833

Davis, A.P. and M.R. Capecchi (1996). A mutational analysis of the 5′ Hox D genes: Dissection of genetic interactions during limb development in the mouse. Development 122:1175-1185. PMID8620844

Capecchi, M.R. (1995). The molecular genetic analysis of mouse development. In Seminars in Developmental Biology. (M.R. Capecchi, Ed.) London: Academic Press 6:233-237.
Zeiher, B.G., E. Eichwald, J. Zabner, J.J. Smith, A.P. Puga, P.B. McCray, Jr., M.R. Capecchi, M.J. Welsh, and K.R. Thomas (1995). A mouse model for the D-F508 allele of cystic fibrosis. J. Clin. Invest. 96:2051-2064. PMID7560099

Davis, A.P., D.P. Witte, H.M. Hsieh-Li, S.S. Potter and M.R. Capecchi (1995). Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature375:791-796. PMID7596412

Manley, N.R. and M.R. Capecchi (1995). The role of hoxa-3 in mouse thymus and thyroid development. Development121:1989-2003. PMID7635047

Capecchi, M. R. (1995). A personal view of gene targeting. In Accomplishments in Cancer Research 1994. (J. G. Fortner and J. E. Rhoads, Ed.) Philadelphia: J. B. Lippincott, pp. 67-78.

Rancourt, D. E., T. Tsuzuki and M. R. Capecchi (1995). Genetic interaction betweeen hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation. Genes Dev. 9:108-122. PMID7828847

Spyropoulos, D. D. and M. R. Capecchi (1994). Targeted disruption of the even-skipped gene, evx1, causes early postimplantation lethality of the mouse conceptus. Genes Dev. 8:1949-1961. PMID7958869

Condie, B. G. and M. R. Capecchi (1994). Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Nature370:304-307. PMID7913519

Davis, A. P. and M. R. Capecchi (1994). Axial homeosis and appendicular skeleton defects in mice with targeted disruption of hoxd-11. Development120:2187-2198. PMID7925020

Kostic, D. and M. R. Capecchi (1994). Targeted disruptions of the murine hoxa-4 and hoxa-6 genes result in homeotic transformations of components of the vertebral column. Mech. Dev. 46:231-247. PMID7918106

Capecchi, M. R. (1994). Targeted gene replacement. Sci. Am. 270:54-61. PMID8134827

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. CONDI PMID7910549

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. Development118:1063-1075. PMID7903632

Capecchi, M. R. (1993). YACs to the rescue. Nature362:205-206. PMID8096325

Deng, C., K. R. Thomas and M. R. Capecchi (1993). Location of crossovers during gene targeting with insertion and replacement vectors. Mol. Cell. Biol. 13:2134-2140.

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. Development117:13-28. PMID8223243

Deng, C. and M. R. Capecchi (1992). Reexamination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus. Mol. Cell. Biol. 12:3365-3371. PMID1321331

Thomas, K. R., C. Deng and M. R. Capecchi (1992). High-fidelity gene targeting in embryonic stem cells by using sequence replacement vectors. Mol. Cell. Biol. 12:2919-2923. PMID1620105

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. Nature355:516-520. PMID1346922

Thomas, K. R., T. A. Musci, P. E. Neumann and M. R. Capecchi (1991). Swaying is a mutant allele of the proto-oncogene Wnt-1. Cell67:969-976. . PMID1835670

Chisaka, O. and M. R. Capecchi (1991). Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature350:473-479. PMID1673020

Capecchi, M. R. (1990). How efficient can you get? Nature348:109. PMID2234072

Capecchi, M. R. (1990). Tapping the cellular telephone. Nature344:105. PMID2308328

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. Nature346:847-850. PMID2202907

Mansour, S. L., K. R. Thomas, C. Deng and M. R. Capecchi (1990). Introduction of a lacZ reporter gene into the mouse int-2 locus by homologous recombination. Proc. Natl. Acad. Sci. USA87:7688-7692. PMID2120706

Capecchi, M. R. (1989). The new mouse genetics: altering the genome by gene targeting. Trends Genet. 5:70-76. PMID2308628

Capecchi, M. R., K. R. Thomas and S. L. Mansour (1989). Creating mice with specific mutations by gene targeting. In Molecular Genetics of Early Drosophila and Mouse Development (M. R. Capecchi, Ed.). Pp. 45-52. Cold Spring Harbor, New York: Cold Spring Harbor Press.

Capecchi, M. R. (1989). Altering the genome by homologous recombination. Science244:1288-1292. PMID2660260

Mansour, S. L., K. R. Thomas and M. R. Capecchi (1988). Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to nonselectable genes. Nature336:348-352. PMID3194019

Thomas, K. R. and M. R. Capecchi (1987). Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503-512. PMID2822260

Wong, E. A. and M. R. Capecchi (1987). Homologous recombination between coinjected DNA sequences peaks in early to mid-S phase. Mol. Cell. Biol. 7:2294-2295. PMID3600663

Thomas, K. R. and M. R. Capecchi (1986). Targeting of genes to specific sites in the mammalian genome. Cold Spring Harbor Symp. Quant. Biol. 51:1101-1113. PMID3472755

Thomas, K. R., and M. R. Capecchi (1986). Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene. Nature324:34-38. PMID3785372

Wong, E. A. and M. R. Capecchi (1986). Analysis of homologous recombination in cultured mammalian cells in a transient expression and a stable transformation assay. Somat. Cell Mol. Genet. 12:63-72. PMID3003931

Thomas, K. R., K. R. Folger and M. R. Capecchi (1986). High frequency targeting of genes to specific sites in the mammalian genome. Cell44:419-428. PMID3002636

Goddard, J. M., J. J. Weiland and M. R. Capecchi (1986). Isolation and characterization of Caenorhabditis elegans DNA sequences homologous to the V-abl oncogene. Proc. Natl. Acad. Sci. USA83:2172-2176. PMID3002636

Wong, E. A. and M. R. Capecchi (1985). Effects of cell cycle position on transformation by microinjection. Somat. Cell Mol. Genet. 11:45-51. PMID3856330

Frels, W. I., J. A. Bluestone, R. J. Hodes, M. R. Capecchi and D. S. Singer (1985). Expression of a microinjected porcine class I major histocompatibility complex gene in transgenic mice. Science228:577-580. PMID3885396

Folger, K. R., K. R. Thomas and M. R. Capecchi (1985). Efficient correction of mismatched bases in plasmid heteroduplexes injected into cultured mammalian cell nuclei. Mol. Cell. Biol. 5:70-74. PMID3982420

Folger, K. R., K. R. Thomas and M. R. Capecchi (1985). Nonreciprocal exchanges of information between DNA duplexes coinjected into mammalian cell nuclei. Mol. Cell. Biol. 5:59-69. PMID2984556

Laski, F. A., R. Belagaje, R. M. Hudziak, M. R. Capecchi, G. P. Norton, P. Palese, U. L. R. Bhandary and P. A. Sharp (1984). Synthesis of an ochre suppressor tRNA gene and expression in mammalian cells. EMBO J. 3:2445-2452. PMID6096120

Folger, K. R., K. R. Thomas and M. R. Capecchi (1984). Analysis of homologous recombination in cultured mammalian cells. Cold Spring Harbor Symp. Quant. Biol.49:123-138. PMID6099232

Young, J. F., M. R. Capecchi, F. A. Laski, U. L. R. Bhandary, P. A. Sharp and P. Palese (1983). Measurement of suppressor transfer RNA activity. Science221:873-875. PMID6308765

Luciw, P. A., J. M. Bishop, H. E. Varmus and M. R. Capecchi (1983). Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Cell33:705-716. PMID6307525

Hudziak, R. M., F. A. Laski, U. L. R. Bhandary, P. A. Sharp and M. R. Capecchi (1982). Establishment of mammalian cell lines containing multiple nonsense mutations and functional suppressor tRNA genes. Cell31:137-146. PMID6760983

Folger, K. R., E. A. Wong, G. Wahl and M. R. Capecchi (1982). Patterns of integration of DNA microinjected into cultured mammalian cells: Evidence for homologous recombination between injected plasmid DNA molecules. Mol. Cell. Biol. 2:1372-1387. PMID6298598

Capecchi, M. R. (1980). High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell22:479-488. PMID6256082

Capecchi, M. R., R. A. V. Haar and M. M. Sveda (1978). Characterization of nonsense mutants in mammalian cells in culture. In Mutations and tRNA Nonsense Suppressors (J. E. Celis and J. D. Smith, Eds.). New York: Academic Press.

Capecchi, M. R., R. A. V. Haar, N. E. Capecchi and M. M. Sveda (1977). Molecular approaches to eucaryotic genetic systems. ICN-UCLA Symposia8:381-398.

Capecchi, M. R., R. A. V. Haar, N. E. Capecchi and M. M. Sveda (1977). The isolation of a suppressible nonsense mutant in mammalian cells. Cell12:371-381. PMID912748

Capecchi, M. R. and R. E. Webster (1975). Bacteriophage RNA as template for in vitro protein synthesis. In RNA Phages (N. D. Zinder, Ed.). Pp. 279-299. Cold Spring Harbor, New York: Cold Spring Harbor Press.

Capecchi, M. R., S. H. Hughes and G. M. Wahl (1975). Yeast super suppressors are altered tRNAs capable of translating a nonsense codon in vitro. Cell6:269-277. PMID802681

Wahl, G. M., S. H. Hughes and M. R. Capecchi (1975). Immunological characterization of hypoxanthine-guanine phosphoribosyl transferase mutants of mouse L cells: Evidence for mutations at different loci n the HGPRT gene. J. Cell Phys. 85:307-320. PMID47331

Hughes, S. H., G. M. Wahl and M. R. Capecchi (1975). Purification and characterization of mouse hypoxanthine-guanine phosphoribosyl transferase. J. Biol. Chem. 250:120-126. PMID237883

Capecchi, M. R., N. E. Capecchi, S. H. Hughes and G. M. Wahl (1974). Selective degradation of abnormal proteins in mammalian tissue culture cells. Proc. Natl. Acad. Sci. USA71:4732-4736. PMID4531013

Sharp, J. D., N. E. Capecchi and M. R. Capecchi (1973). Altered enzymes in drug resistant variants of mammalian tissue culture cells. Proc. Natl. Acad. Sci. USA70:3145-3149. PMID4522295

Klein, H. A. and M. R. Capecchi (1971). Polypeptide chain termination, purification of the release factors, R1 and R2 from Escherichia coli. J. Biol. Chem. 246:1055-1061. PMID5543670

Capecchi, M. R. and H. A. Klein (1970). Release factors mediating termination of complete proteins. Nature26:1029-1033. PMID4911223

Capecchi, M. R. and H. A. Klein (1969). Characterization of three proteins involved in polypeptide chain termination. Cold Spring Harbor Symp. Quant. Biol. 28:469-477. PMID4909514

Capecchi, M. R. (1967). Polarity in vitro. J. Mol. Biol. 30:213-217. PMID6077936

Capecchi, M. R. (1967). Polypeptide chain termination in vitro: Isolation of a release factor. Proc. Natl. Acad. Sci. USA58:1144-1151. PMID5233840

Capecchi, M. R. (1967). A rapid assay for polypeptide chain termination. Biophys. Res. Comm.28:773-778. PMID6061555

Capecchi, M. R. (1967). Polycistronic messenger RNA and the phenomenon of suppression, BBA Library. In Regulation of Nucleic Acid and Protein Synthesis (V. V. Konigsberger and L. Bosch, Ed.), Vol. 10, pp. 243-258. Amsterdam: Elsevier Publishing Co.

Gussin, G. N., M. R. Capecchi, J. M. Adams, J. E. Argetsinger, J. Tooze, K. Weber and J. D. Watson (1966). Protein synthesis directed by RNA phage messengers.Cold Spring Harbor Symp. Quant. Biol. 31:257-271. PMID4866373

Bergquist, P. L. and M. R. Capecchi (1966). Fractionation of a suppressor tRNA. J. Mol. Biol.19:202-206. PMID5338521

Capecchi, M. R. (1966). Cell-free protein synthesis programmed with R17 RNA: Identification of two phage proteins. J. Mol. Biol. 21:173-193. PMID5969761

Capecchi, M. R. (1966). Initiation of E. coli proteins. Proc. Natl. Acad. Sci. USA55:1517-1524. PMID5336288

Adams, J. M. and M. R. Capecchi (1966). N-formylmethionine-tRNA as the initiator of protein syntheses. Proc. Natl. Acad. Sci. USA55:147-155. PMID 5328638

Capecchi, M. R. and G. N. Gussin (1965). Suppression in vitro: Identification of a serine-tRNA as a “Nonsense Suppressor.” Science149:417-422. PMID17809404

Principal Investigator

null

Mario Capecchi

Nobel Laureate

Lab

null

Amir Pozner

null

Anne Boulet

null

Ben Xu

null

Carol Lenz

null

Emanuele Panza

null

Erik M. Peden

null

Hyung Song Nam

null

Kay Higgins

null

Naveen Nagarajan

null

Petr Tvrdik

null

Rick Focht

null

Sheila Barnett

null

Shrutokirti De

null

Simon Titen

null

YuanYuan Wu

null

Kiramey Gilleese

Former Lab Members

null

Matthew Hockin

Address

MARIO R. CAPECCHI, PH.D.
HOWARD HUGHES MEDICAL INSTITUTE
University of Utah
15 North 2030 East rm. 5440
Salt Lake City, UT 84112-5331

Phone

801-581-7096

Fax

801-585-3425