Beschreibung

• The mouse, including countless lines of transgenic and knockout mice, has become the most prominent model organism in biomedical research. Behavioural characterization is often conducted in batteries of short tests on locomotion, anxiety, learning and memory, etc. In such tests, any individual differences within groups are usually considered to be disturbing variance. To reduce such variance in experimental animal research enormous efforts at standardization have been made, e.g., by using inbred lines to minimize genetic variability. However, while a substantial reduction of variability has been reached a considerable amount of inter-individual differences still seems to escape all efforts of standardization. Interestingly, many behavioural patterns of individual animals are significantly correlated across contexts and time. In evolutionary biology, 'animal personalities' have been discussed recently to comprise such stable patterns. I argue here, that non-random behavioural correlations across contexts and time might underlie the variability commonly found in biomedical mouse studies. The establishment of such 'personality' like traits constitutes a reduction of phenotypic plasticity, since subjects exhibiting an 'animal personality' act and react differently in different contexts and according to their behavioural history. In this project, laboratory mice will be used as model system to systematically analyse such a reduction of phenotypic plasticity in response to defined variation of genetic and environmental parameters. Female mice from two inbred strains and the progeny of inter-crosses of the two strains up to the second filial generation will be analyzed. This will vastly expand our knowledge whether or not genetic variability is a prerequisite for the establishment of 'animal personality'. Apart from experimentally varying genetic heterogeneity, environmental challenges will be applied in separate experiments. The effects of variations during the early postnatal phase on the reduction of phenotypic plasticity will be tested by comparing genetically identical mice that either received high or low maternal care. Finally, it will be tested by repeated re-composition of social groups during adolescence or adulthood, if adolescence indeed opens a special time frame of re-modulation of phenotypic plasticity, or if such modulation can also occur easily later in life. The characterization of the mice in each experiment will be done by means of a multifaceted long term approach: over the course of 26 weeks three repeats of a behavioural test battery, analysis of stress hormones, constant activity monitoring, and an in depth automated behavioural characterization including tests for cognitive skills will be accomplished. Overall the extensive data set derived from these analyses will broaden our knowledge whether or not and to what extent genetic and environmental variability affects the plasticity of behavioural phenotypes later in life.

Projektlaufzeit

• 01.05.2014 - 31.12.2016

Ergebniszusammenfassung

• The mouse, including countless lines of transgenic and knockout mice, has become the most prominent model organism in biomedical research. Behavioural characterization is often conducted in batteries of short tests on locomotion, anxiety, learning and memory, etc. In such tests, any individual differences within groups are usually considered to be disturbing variance. Despite of an enormous efforts of standardization a considerable amount of inter-individual differences persist. In this project we demonstrate that individual differences can reasonably be discussed as 'animal personalities'. We are especially interested in how such these traits develop over the life time of individual mice since long term observations in mice are surprisingly rare. The experimental design includes female mice from two inbred strains and the progeny of intercrosses of the two strains up to the second filial generation. These mice are observed in their behavioural development over the course of 26 weeks. During this period of time three repeats of a behavioural test battery, analysis of stress hormones, constant activity monitoring, and an in depth automated behavioural characterization including tests for cognitive skills in IntelliCages are accomplished. The analysis of the large data set derived from these experiments is currently still being carried out. First results confirm animal personality like traits and individual differences that escape all efforts of standardisation. Furthermore, our data backs up strong parent-of-origin as well as early postnatal environment effects on the phenotypes later in life. Genetic diversity seems to increase the repeatability over time. Further analysis of gene and environmental contributions to the reduction of phenotypic plasticity is still being carried out. In a complementary approach we observed the behavioural development of male inbred mice from birth to death focussing on individual differences in relation to cognitive demands. To our knowledge this is the first time that mice are systematically observed throughout their entire life and this data will contribute significantly to the understanding of the reduction of phenotypic plasticity. Immer vorneweg! – Von Leithammeln und Alphatieren, Interview mit Lars Lewejohann in der SWR2 Matinee, 24.4.16, https://goo.gl/GYPFGe. Unerhört. Können sich Tiere unterhalten?, Beitrag von Lars Lewejohann zum 8. Osnabrücker Wissensforum 2015, https://goo.gl/5JiPMc. How does individuality develop?, Hannah Critchlow on "The Naked Scientists", 20.05.2013, https://goo.gl/UkW5Ae. Faulpelze, Angsthasen und schräge Vögel, Ina Schicker in Bild der Wissenschaft online 2011, https://goo.gl/OfCltp