The primary interest of the Unité de Génétique des Mammifères is in the mouse as a model organism. Some 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 are undertaken to clone the genes involved. The Unit has recently undertaken investigations aimed at a better understanding of the genetic determinism of susceptibility/ resistance to infectious diseases by using a new kind of inbred strains (interspecific recombinant congenic and consomic strains).

The unité de Génétique des Mammifères focuses on four main research topics:

1. Positional cloning of mouse mutations with deleterious effects on the mammalian development.
Three mutations are now in the process of being cloned: digitation anormale (dan - Mrs Dominique Simon), which is impairing the normal process of digitation and limb development; progressive motor neuronopathy (pmn - Mrs Natalia Martin and Mr Jean Jaubert) having a dramatic effect on the control of moto-neurone integrity, fragilitas ossium (fro — Miss Isabelle Aubin) which is responsible for an abnormal bone development.

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 by the flavivirus West Nile. A gene, with a major effect is now being cloned. Investigations in this matter are conducted in cooperation with several research teams at the Institut Pasteur in the frame of Transverse Research Programme (TRP 21 - Coordinator: Mr P. Desprès). In the unité de Génétique des Mammifères, this subject is dealt with by Mr Tomoji Mashimo and Mrs Dominique Simon.

3. The unité de Génétique des Mammifères has developed inbred strains of a new kind that represent excellent tools for the analysis of genetic determinism of complex or multigenic traits. These strains have a genome which is made out of a very unequal contribution of the genome of two different species of the genus Mus (Mr Xavier Montagutelli, Mr Marek Szatanik and Mr Jean-Louis Guénet).

4. The unité de Génétique des Mammifères is also interested in the identification of genes whose action is to modulate the expression of a mutation with a deleterious phenotype. A mouse model of erythropoietic protoporphyria (mutation Ferrochelatase deficiency - Ms Abitbol and Mr Xavier Montagutelli) is being investigated as an example for the action of modifier genes.

In addition to its scientific activity the unité de Génétique des Mammifères performs, as a service, genetic mapping of cloned DNA sequences for scientists requesting this information.

FLEURANCE Isabelle, IP, ifleur@pasteur.fr

MONTAGUTELLI Xavier, IP, xmonta@pasteur.fr

MASHIMO Tomoji, postdoctoral

SZATANIK Marek, IP