Cracking anxiety in the mouse: a quantitative (epi)genetic approach

The aim of this thesis was to improve existing methodologies and apply genetic strategies in order to identify (main-effect, epistatic, multiple and pleiotropic) quantitative trait loci and to decipher functional candidate genes for anxiety-related behavior and baseline blood plasma total cholesterol level on mouse chromosome 19. In addition, environmental, epigenetic and other influences on anxiety-related behavior were investigated, such as magnesium deficiency, sex differences, substrain differences and parent-of-origin effects. The modified Hole Board (mHB), a behavior test for measuring anxiety-related behavior in laboratory mice, was described in detail (Chapter 2), in accordance with the ARRIVE guidelines. Further, methods for reporting and studying genetic influences were improved (Chapters 3 & 6). In addition, external influences (dietary Mg level, Chapter 4; light regime, Chapters 4 & 5) on anxiety-related behavior were identified, physiological influences (body weight gain, circulating corticosterone level, brain and blood plasma Mg concentration) on anxiety were measured (Chapter 4) and sex differences (Chapters 6 & 7) as well as parent-of-origin effects (Chapter 7) were described. These influences were taken into account and partly incorporated (i.e. sex and parent-of-origin) in the genetic strategies used to identify quantitative trait loci (QTLs) for anxiety-related behavior and its possible pleiotropic connection to the QTL(s) for baseline circulating total cholesterol (Chapters 8 & 9). In sum, the work in the present thesis has improved our understanding of anxiety-related behavior, by applying improved methodologies and identifying (genetic) factors involved in this process.