Mouse functional Genetics - URA CNRS 2578 / USC INRA 2026  


  HEADPANTHIER Jean-Jacques / panthier@pasteur.fr
  MEMBERSDr. AUBIN-HOUZELSTEIN Geneviève / Dr. BECK-CORMIER Sarah / Mle BLANCHET Charlène / Dr. BURGIO Gaëtan / Dr. COHEN-TANNOUDJI Michel / Mle DJIAN Johanna / Dr. EGIDY-MASKOS Giorgia / Mle FENINA Myriam / Mme FLEURANCE Isabelle / M. GUILLEMOT Laurent / Dr. HOULARD Martin / Dr. JAUBERT Jean
M. LEGUILLIER Teddy / Dr. MONTAGUTELLI Xavier / Prof. PANTHIER Jean-Jacques / Dr. SIMON Dominique / Mle SOUILHOL Céline / Mme VANDORMAEL-POURNIN Sandrine / Dr. ZAVERUCHA DO VALLE Tânia


  Annual Report

The Mouse Functional Genetics laboratory has been established in May, 2005. The research programmes focus on two main topics within the fields of activity of the Institut Pasteur:

- Genetic mechanisms of susceptibility to infectious diseases.

- The biology of embryonic and adult stem cells.

Genetics of susceptibility to infection diseases

An outgrowth of concern about newly emerging and re-emerging diseases and the progressive development of antibiotic-resistant pathogens justifies increased interest in infectious disease research. The clinical outcome of infectious diseases is determined by complex interactions between the pathogen and the genome of affected individuals, under the influence of environmental and stochastic factors. To identify genetic mechanisms of susceptibility to infectious diseases, mouse models are essential. Actually, experimental standardised infection of mice from controlled mating between inbred strains, bred in specific-pathogen-free conditions, with a given dose of pure inoculum offers a powerful approach. This approach eliminates several sources of environmental variance hence making easier the identification of genes influencing host susceptibility. We focus our research on few life-threatening micro-organisms, including Yersinia pestis, the agent of Plague, West Nile virus, responsible for fatal encephalitis, and the Rift Valley fever virus, responsible for hemorrhagic fever.

Biology of embryonic and adult stem cells

Stem cells are capable of both generating identical progeny, and producing transit amplifying cells (TA-cells) committed to differentiate. Regulation of the number of stem cells, TA-cells and differentiated cells is a crucial problem in multicellular organisms. Defects in stem cell renewal may lead to lineage disappearance or cancer. Indeed, tissues and organs in the embryo and in the adult rely heavily on homeostasis, where, as cells die accidentally or naturally, they are replenished. Many of the features that govern the behavior of stem cells remain unknown. Our research takes advantage of various mouse lines carrying spontaneous or targeted mutations in a number of genes, including Notchless, Strawberry notch 2 and Omcg1, to study the cellular and molecular basis of stem cell renewal and maintenance, and its differentiation into TA-cell and mature cell. Our research focus on the study of the early embryo and melanogenesis using the mouse as an experimental model.

Keywords: experimental infectious, innate response, arbovirus, zoonosis, Yersinia pestis, resistance/susceptibility, Notch signaling pathway, cell cycle, ES cells, early embryo, stem cells, melanocyte

Gfs.jpg

A novel transgenic mouse reporter line allows the assess­ment of Notch signalling dynamics and regulation in vivo.



  Publications

  • Monet, M., V. Domenga, B. Lemaire, C. Souilhol, F. Langa, C. Babinet, T. Gridley, E. Tournier-Lasserve, M. Cohen-Tannoudji, and A. Joutel. 2007. The archetypal R90C CADASIL-NOTCH3 mutation retains NOTCH3 function in vivo. Hum Mol Genet 16:982-92. 17331978.

  • Burgio, G., M. Szatanik, J. L. Guenet, M. R. Arnau, J. J. Panthier, and X. Montagutelli. 2007. Interspecific Recombinant Congenic Strains Between C57BL/6 and Mice of the Mus spretus Species: A Powerful Tool to Dissect Genetic Control of Complex Traits. Genetics 177:2321-33. 17947429.

  • Cormier, S., S. Le Bras, C. Souilhol, S. Vandormael-Pournin, B. Durand, C. Babinet, P. Baldacci, and M. Cohen-Tannoudji. 2006. The murine ortholog of Notchless, a direct regulator of the Notch pathway in Drosophila melanogaster, is essential for survival of inner cell mass cells. Mol Cell Biol 26:3541-9. 16611995.

  • Abitbol, M., F. Bernex, H. Puy, H. Jouault, J. C. Deybach, J. L. Guenet, and X. Montagutelli. 2005. A mouse model provides evidence that genetic background modulates anemia and liver injury in erythropoietic protoporphyria. Am J Physiol Gastrointest Liver Physiol 288:G1208-16. 15677551.

  • Artus, J., S. Vandormael-Pournin, M. Frodin, K. Nacerddine, C. Babinet, and M. Cohen-Tannoudji. 2005. Impaired mitotic progression and preimplantation lethality in mice lacking OMCG1, a new evolutionarily conserved nuclear protein. Mol Cell Biol 25:6289-302. 15988037.



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Activity Reports 2007 - Institut Pasteur
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