This international research project aims to generate, characterize, and validate transgenic rat models of two neurodegenerative diseases: Huntington disease (HD) and spinocerebellar ataxia type 17 (SCA17). Besides traditional methods of analysis of behavioral data, new methods are being developed to enable behavioral classification of transgenic and wild type animals. This enables the detection of early onset of specific symptoms and provides read-out parameters in pre-clinical studies applying novel substances for the treatment of HD and SCA17. Last but not least, these read-outs are validated in a gene therapy study with SCA17 rats using Antisense Oligonucleotides (AONs) against the PolyQ stretch of TBP.
Noldus is one of the partners in this international consortium. In this project, PhenoTyper cages are connected to computer systems running EthoVision XT software to facilitate automated trial control and operant testing, and the analysis of behavioral observations through video tracking. Behavioral phenotyping using a unique combination of fully automated continuous observation, experimentation and analysis is applied in this project. CatWalk XT gait analysis system also plays an important role. Rat models are also tested (HD/SCA17).
This approach allows objective collection and sophisticated analysis of behavioral data in a novel paradigm, based on long-term fully automated observation in an enriched home cage environment. This results in a very rich behavioral data set, bringing to light effects of pharmacological treatment or genetic differences not obscured by stress (novelty, transport and handling) induced inhibition.
Noldus has extensive knowledge about tracking and analysis of rodent behavior with EthoVision XT and the Rat Behavior Recognition Module. In this project Noldus supervises three PhD fellows as they develop of new algorithms and software tools for tracking and analysis of rodent behavior in a social context, as well as novel analysis methods and statistical algorithms to relate this behavior to the HD and SCA17 phenotypes.
PhenoRat is a unique consortium in which industry (Noldus Information Technology), academia (Utrecht University, Raboud University, and University of Tuebingen), and a university-related foundation for entrepreneurship (StartLife,) work closely together to achieve both organization of an excellent training program and performance of excellent research projects with a pronounced focus on inter-sectoral doctoral education and transfer of knowledge.
- Raboud University, The Netherlands
- Noldus Information Technology, The Netherlands
- StartLife, The Netherlands
- University of Tuebingen, Germany
- Utrecht University, The Netherlands
Elisavet I. Kyriakou, Jan van de Kieft, Huu P. Nguyen, Johanneke E. van der Harst (2014). Defining Parameters in Automated Quantitative Gait Analysis for Evaluation of Progressive Neurodegeneration in Animal Models of Ataxia and Motor Coordination Impairments. Proceedings of Measuring Behavior 2014, (Wageningen, The Netherlands, August 27-29, 2014). Editors: A.J. Spink, L.W.S. Loijens, M. Woloszynowska-Fraser & L.P.J.J. Noldus. www.measuringbehavior.org.
PhenoRat is funded from the European Community‘s Seventh Framework Programme FP7/2012 under grant agreement No. 317259.