Unit: Mammalian Genetics - URA CNRS 2578
Director: Xavier Montagutelli
The interest of the Unité de Génétique des Mammifères is in the mouse as a model organism for studying several human diseases with genetic determinism. Specific mutations, with deleterious effects on the neuromuscular system, the integument and its derivatives or the bone tissue are under investigation at the molecular level and experiments have been undertaken to clone the relevant genes. The Unit has also undertaken investigation aimed at a better understanding of the genetic determinism of susceptibility/ resistance to infectious diseases, with special emphasis on the innate mechanisms of defence. Finally, the Unité has developed a series of tools to help in the analysis of traits with a complex determinism (interspecific recombinant congenic and consomic strains).
The unité de Génétique des Mammifères focuses its scientific activity on four main topics:1. Positional cloning of four mouse mutations with deleterious effects:
- digitation anormale and malformed digits (dan mdig - Mrs Dominique Simon), two recessive mutations that impairs the normal process of digit development;- paralysé and frissonnant (par and fri - MM Asadollah Aghaie, Jean Jaubert and Marek Szatanik) two mutations with severe effects on the motoneurons.- fragilitas ossium (fro - Miss Isabelle Aubin) a mutation that leads to a severe form of juvenile osteogenesis imperfecta.
2. The unité de Génétique des Mammifères is also interested in the analysis of the genetic determinism of susceptibility/resistance of mice to experimental infections with several pathogens. A gene with a major effect on the susceptibility to the West Nile flavivirus has been identified and is being analysed (2'-5' OAS). Mrs Dominique Simon is currently preparing a series of transgenic mice with the aim to analyze the function of individual Oas genes. Susceptibility of mice to Yersinia pestis and Helicobacter pylori is also being considered (M. Marek Szatanik). These investigation are conducted in cooperation with other research teams at the Institut Pasteur. 3. The unité de Génétique des Mammifères is also interested in the identification of modifier genes whose action is either to alleviate or to worsen the phenotypic expression of a mutation with a deleterious phenotype. A mouse model of erythropoietic protoporphyria is being investigated as an example for the action of modifier genes (mutation Ferrochelatase deficiency - Ms Abitbol and M. Xavier Montagutelli).4. The unité de Génétique des Mammifères has developed inbred strains of a new kind that represent powerful tools for the analysis of the determinism of complex or multigenic traits. The genome of these strains results from a very unequal contribution of two parental strains belonging to two different species of the genus Mus: Mus spretus (strain SEG/Pas) the donor strain (2-4%) and C57BL/6, the background strain (96-98%). Analyzing the phenotype of these strains for any trait that is different in the parental strains may help in the localization of the relevant genes (MM. Xavier Montagutelli, Gaëtan Burgio and Marek Szatanik).
Keywords: mice, mutations, models, quantitative genetics, susceptibility to experimental infections