The explorative-reduced (EXR002) C3H mice–a new mouse model of depression?

Phenotype-driven analysis of mouse mutants complement gene-driven analysis of genetically modified animals. During large screening program, initiated by the ethyl-nitrosourea (ENU)-mutagenesis program to find new behavioral phenotypes, a single mouse was identified, which exhibited reduced explorative behavior in the modified hole board (mHB) test. After several generations of breeding, the offspring of this mouse showed a stable phenotypic penetrance. The explorative-reduced (EXR002) C3H mice showed in the modified hole board (mHB) test significantly reduced explorative behavior compared to the C3H wildtype strain. The mHB test, a combination of elements of the hole board and the open field test, allows to detect and analyze a wide range of behaviors, including anxiety-related behavior, risk assessment, locomotion, arousal, social affinity, cognition and exploration strategies (Ohl et al., 2003). Exploration includes such behaviors as risk assessment, walking, climbing, sniffing, manipulation of objects and rearing (Kelley, 1993). EXR002 C3H mice differ also markedly from wildtype C3H mice in their inborn acute stress coping strategy. They showed more immobility and less struggling in a modified version of the Porsolt forced swim test, in which changes towards more active coping strategies have frequently been shown to predict the antidepressant efficacy of drug when administered to patients suffering from depression.