Mario Capecchi

Distinguished Professor and Co-Chair of Human Genetics and Professor of Biology

2007 Nobel Prize Winner for Physiology or Medicine

 

Mario Capecchi

B.S. Antioch College

Ph.D. Harvard University

Research

References

 

 

Research

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 and cancer. 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. Eventually, this technology should also provide an avenue for directly correcting genetic defects in humans via somatic gene therapy.

 

References

1. Haldar M, Hancock JD, Coffin CM, Lessnick SL, Capecchi MR (2007) A conditional mouse model of synovial sarcoma:  insights into a myogenic origin.  Cancer Cell. Mar. 11(4)

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

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

4. Keller CB, Capecchi MR (2005) New Genetic Tactics to Model alveolar Rhabdomyosarcoma in the Mouse.  Cancer Res. Sept. 1;65(17):7530-32

5. Kindlmann GL, Weinstein DM, Jones GM, Johnson CR, Capecchi MR, Keller C (2005) Practical vessel imaging by computed tomography in live transgenic mouse models for human tumors.  Molecular Imaging Oct-Dec; 4(4):417-24

6.  Arenkiel BR, Tvrdik P, Gaufo GO, Capecchi MR (2004) Hoxb1 functions in both motoneurons and tissues of the periphery to establish and maintain the proper neuronal circuitry.   Genes Dev. 18:1539-1552

7. Boulet AM, Moon AM, Arenkiel BR, Capecchi MR (2004) The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth.   Dev. Biol. 273:361-372

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

9. Gaufo GO, Wu S, Capecchi MR (2004) Contribution of Hox genes to the diversity of the hindbrain sensory system.   Development 131:1259-1266

10. Boulet AM, Capecchi MR (2004) Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod.   Development 131:299-309

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

12. Barrow JR, Thomas KR, Boussadia-Zahui O, Moore R, Kemler R, Capecchi MR, McMahon AP (2003) Ectodermal Wnt3/ b -catenin signaling is required for the establishment and the maintenance of the apical ectodermal ridge.   Genes Dev . 17:394-409

13. Vorbach C, Scriven A, Capecchi MR (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

14. Wellik DM, Hawkes PJ, Capecchi MR (2002) Hox11 paralogous genes are essential for metanephric kidney induction.   Genes Dev . 16:423-1432

13. Hobbs NK, Bondareva AA, Barnett S, Capecchi MR, Schmidt EE (2002) Removing the vertebrate-specific TBP N-terminus disrupts placental b 2m-dependent interactions with the maternal immune system.   Cell 110:43-54

15. Greer JM, Capecchi MR (2002) Hoxb8 is required for normal grooming behavior in the mouse.   Neuron 33:23-34

16. Capecchi MR (2001) Generating mice with targeted mutations.   Nature Med. 7:1086-1090

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

18. Gaufo GO, Flodby P, Capecchi MR (2000) Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways.   Development 127:5343-5354

19. Schmidt EE, Taylor DS, Prigge JR, Barnett S, Capecchi MR (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids.   Proc. Natl. Acad. Sci. USA 97:13702-13707

20. Greer JM, Puetz J, Thomas KR, Capecchi MR (2000) Maintenance of functional equivalence during paralogous Hox gene evolution.   Nature 403:661-665

21. Barrow JR, Stadler HS, Capecchi MR (2000) Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse.   Development 127:933-944