The Team
  • Researchers


    Véronique BRAULT


    Virginie HAUSHALTER

    Yann HERAULT

    Michel ROUX

  • Post-Doctoral Fellows


    Maria del Mar MUNIZ MORENO

  • PhD Students

    Hélin ATAS-OZCAN

    Céleste CHIDIAC

    Alexandra JIMENEZ ARMIJO

    Marion PELLEN

    Ameer Abu Bakr RASHEED

    Yaping XUE

  • Engineers & Technicians

    Claire CHEVALIER

    Arnaud DUCHON

    Valérie HERAULT

    David REISS

Translational medicine and neurogenetics

Physiopathology of aneuploidy, gene dosage effect and Down syndrome

Our aim is to better understand the physiopathology of aneuploidies and other genetic diseases with Intellectual Disabilities (ID), using mouse models. Identifying dosage- sensitive genes and deregulated pathways will increase our knowledge of ID and will allow therapeutic intervention in preclinical models.

Initially we focused our interest on Down syndrome (DS), a frequent aneuploidy affecting 1 newborn out of 700, identified as the consequence of Trisomy 21. Our approach led to a better definition of the phenotypic-genotypic map with the identification of genes or genetic regions associated with cognition, heart defect and craniofacial changes. We also found that the presence of an additional copy of mouse genomic regions homologous to Hsa21 was able to influence the expression of the whole genome.


We identified deregulated pathways and two dosage-sensitive genes involved in learning and memory defects. We also developed a preclinical approach to rescue the cognitive defects observed in DS models. We validated several drugs, targeting the GABAergic neurotransmission or the kinase activity of Dyrk1a to improve cognition in preclinical models. Two of these drugs are now under clinical evaluation in human and we are continuing to work on their mechanisms of action, as well as exploring drugs targeting a new candidate gene.


We have started to explore behaviour and cognition in other mouse models of ID. We have expended our array of tests to assess more precisely cognition, learning and memory and social behaviour. We are also using imaging with expert groups in the field from Strasbourg and elsewhere to detect structural and functional changes in the brain. In parallel, we are building bridges with Medical geneticists in Strasbourg and in Europe to compare human and mouse phenotypes associated with IDs.
Cellular basis of the defects associated with ID are explored using combined approaches of mouse genetics and phenotyping, cell culture, and conditional genetic manipulations using Cre/loxP system, Adeno-virus Associated virus or CrispR/Cas9 technologies. We are implementing integrative approaches, combining standardised phenotypic data, expression analysis (RNAseq and quantitative proteomics) with epigenetic approaches to better understand the molecular changes observed in ID.


We have set up with the PHENOMIN-ICS and the GENCODYS European funder project a unique ID zoo with more than 60 mouse models. We are now investigating ageing and cognition in normal and pathological conditions while contributing to the AGEDBrainsysbio Eu funded project.

Imprimer Envoyer

Université de Strasbourg

IGBMC - CNRS UMR 7104 - Inserm U 1258
1 rue Laurent Fries / BP 10142 / 67404 Illkirch CEDEX / France Tél +33 (0)3 88 65 32 00 / Fax +33 (0)3 88 65 32 01 /