WP 02 – Animal Model Development

Objectives

The goal of this workpackage is to identify the most suitable animal models for ASD. There are four main objectives that are jointly directed towards defining molecular and physiological alterations and the most appropriate behavioural endpoints relevant to ASD.

  • Provide rodent models with construct and face validity for ASD
  • Develop and validate behavioural assays for the core symptoms of ASD
  • Identify neuronal circuit deficits in ASD models and biomarkers
  • Employ ASD models and behavioural assays to test pharmacological intervention strategies

WP Leads

Academic Lead: Prof. Dr. Peter Scheiffele, Biozentrum, University of Basel, Switzerland

EFPIA lead: Dr. Thomas Steckler, Janssen Pharmaceutica, Belgium

Workpackage partners

  • Biozentrum, University of Basel
  • Janssen Pharmaceutica
  • F. Hoffmann- La Roche
  • University Medical Centre
  • Institut Pasteur
  • Max-Planck-Gesellschaft
  • Eli Lilly and Company Ltd.
  • Institut de Recherches Servier
  • Vifor Pharma
  • Pfizer Limited
  • University Ulm
  • Neurosearch

Workpackage outcomes

This Workpackage will deliver:

  • Rational prioritization of ASD animal models for further study, a common resource of ASD animal models for sharing between participants, an evaluation of reproducibility of VPA and double-hit models at multiple sites,  and a novel genetic rescue animal model for ASD.
  • Expert consensus on the most suitable behavioral assays and protocols, an evaluation of assay reproducibility across sites, novel standardized and automated behavioral paradigms for mouse models of ASD, and an evaluation of behavioral phenotypes in selected mouse mutants.
  • Comparative gene expression profile analysis in rodent ASD models, biomarker signatures of rodent ASD models,  identification of neuronal circuit and physiological alterations in ASD models, recommendation on targets to be used for pharmacological intervention and  forward and reverse translation of findings between preclinical and clinical studies.
  • Assessment of reversibility of neurodevelopmental defects in ASD models, recommendation of the most suitable tool compounds to be tested in ASD models, Recommendation of most suitable animal models and assays for pharmacological testing, Assessment of success of pharmacological interventions with select tool compounds.
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