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High-throughput, fully automated and cost-effective behavioural phenotyping of normal, clinical and genetic mouse models

Final Report Summary - INTELLIMAZE (High-throughput, fully automated and cost-effective behavioural phenotyping of normal, clinical and genetic mouse models)

This SME project brought together three SMEs and four academic partners for developing and validating a compact, economic and fully automated modular platform, called INTELLIMAZE, that will permit both high-throughput and detailed behavioural characterisation of current and future mouse models in biomedicine. The technical development was done by two SMEs (NewBehavior, and Frank Buschmann International) and one academic partner (Anokhin Institute of Normal Physiology of the Russian Medical Academy of Science).

The commercial objective was to obtain a significant market share of the developing market of automated test systems, and to tailor such systems for small biotech SMEs in need of behavioural characterisation. The joint scientific objectives of the academic partners were validation of this novel technology and inter-laboratory standardisation.

The final goal was a fully automated behavioural test system for mice inside a home cage, and outside in traditional test arenas, working without supervision and outputting data in familiar format and ready for statistics. Moreover, cross-laboratory standardisation was achieved with minimal efforts and animal welfare guaranteed. In order to achieve better market penetration, NewBehavior has concluded a distribution agreement with another SME (TSE Systems Germany), thus realising one of the objectives of the STRE/SME FP6 programme.

Technically, this project has fulfilled all expectations: the mouse testing community in industry and academia has now a tool that permits fully automated mouse testing, even with a minimum of behavioural knowledge. IntelliCages themselves represent an extremely efficient high-throughput tool for testing large numbers of mice in a minimum of time.

Their unmatched advantage is a standardisation of the environment and testing procedures. The most economical way of use is screening for long-lasting or slowly changing behavioural alterations induced by genetic engineering, toxicants, neurological and any form of somatic diseases, as well as developmental, social and environmental manipulations. The INTELLIMAZE add-ons provide the ability to expand the IntelliCage system, enabling it - using the same software - to conduct behavioural tests requiring larger arenas, to measure food consumption and to quantify social behaviour. In the form presented here, the combined systems could replace about 90 % of behavioural tests that are traditionally employed.

Commercially, the availability of a system with pre-programmed mouse-adapted modules for specific needs and questions makes the system suitable not only for specialised phenotyping laboratories but even for small biotech companies lacking behavioural expertise and wishing to screen the effects of novel drug compounds.

The cross-European comparisons between different user laboratories have shown a high comparability of genetically dependent behaviour of mice. Notably, the inherent variability due to social interactions does not mask the strain differences. In technical terms, the minor variations induced by social interactions prevent one of the disadvantages of total standardisation, namely unpredictable effects of subtle idiosyncrasies in the testing environment. Therefore, the systems provide a high level of equivalence in test results.

Comparing the many mouse models of neurodegenerative diseases is thus greatly facilitated by using IntelliCage and INTELLIMAZE systems. Scientifically, the project has resulted in a large data set referencing the effects of brain lesions to standard tests for impaired hippocampal, prefrontal and striatal functions. Therefore, it is possible to classify behavioural phenotypes of many mouse models as discovered by IntelliCage and INTELLIMAZE according to the potential involvement of these structures. In addition, the project has generated novel approaches to study depression in mice and to quantify deficits in social behaviour characteristic for autism and schizophrenia in humans.

From the viewpoint of animal welfare, both IntelliCage and INTELLIMAZE contribute significantly to the 3R principle: replace, reduce, refine. The systems anticipate the legislative trend towards more stringent regulations in the field of animal testing systems. Not only they offer minimal handling by experimenters, but also a social and enriched environment yet permitting to conduct almost any type of behavioural experiments.