Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences.

Myg1 (Melanocyte proliferating gene 1) is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization. In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. To study the effects of Myg1 loss-of-function, we created Myg1-deficient (-/-) mice by displacing the entire coding sequence of the gene. Initial phenotyping, covering a multitude of behavioural, cognitive, neurological, physiological and stress-related responses, revealed that homozygous Myg1 (-/-) mice are vital, fertile and display no gross abnormalities. Myg1 (-/-) mice showed an inconsistent pattern of altered anxiety-like behaviour in different tests. The plus-maze and social interaction tests revealed that male Myg1 (-/-) mice were significantly less anxious than their wild-type littermates; female (-/-) mice showed increased anxiety in the locomotor activity arena. Restraint-stress significantly reduced the expression of the Myg1 gene in the prefrontal cortex of female wild-type mice and restrained female (-/-) mice showed a blunted corticosterone response, suggesting involvement of Myg1 in stress-induced responses. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice. Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences.

Behavioural differences between C57BL/6 and 129S6/SvEv strains are reinforced by environmental enrichment.

Housing in enriched environment has been advocated as a means for controlled variation of environmental conditions in transgenic studies to explore interactions between genes and surroundings. In the present study, behavioural phenotypes of C57Bl/6 (B6) and 129S6/SvEv (129) mice, housed in either standard laboratory conditions or environmentally enriched conditions, were explored. Housing in enriched conditions increased exploratory activity in the plus-maze and reduced habituation in the locomotor activity test in B6 mice, whereas in 129 mice increased hot plate latencies and reduced aggression were observed. Compared to B6, 129 strain displayed lower exploratory activity in the plus-maze and locomotor activity test, longer hot plate latencies, spent more time immobile in the forced swim test and engaged more in social interaction. These behavioural differences between the two strains were reproducible independent of pre-experimental housing conditions. Moreover, environmental enrichment accentuated dissimilarities between the strains in the plus-maze, locomotor activity, hot plate and forced swim test. By contrast, strain differences in anxiety-like behaviours in the plus-maze test and in aggressive encounters in the resident-intruder test were not reproducible in mice housed in alternative environmental conditions, suggesting a strong contribution of environmental factors to the development of these phenotypes. It is concluded that the application of environmental enrichment in addition to standard housing conditions is a meaningful approach for testing reproducibility of behavioural findings within one laboratory.

Different housing conditions alter the behavioural phenotype of CCK(2) receptor-deficient mice.

The behavioural phenotype of mice, lacking CCK(2) receptors, has varied across studies conducted not only in different laboratories, but also across studies published by the same laboratory. The present study was designed to elucidate the phenotype of CCK(2) receptor-deficient mice housed in two different environmental conditions within the same laboratory. Environmental enrichment was used as an alternative environment to standard laboratory conditions. Significant genotype by environment interaction was observed in the plus-maze, hot-plate, restraint-induced analgesia and water maze test. While mice, lacking CCK(2) receptors, housed in standard conditions were more anxious, displayed stronger restraint-induced analgesia and performed worse in the water maze when compared to corresponding wild-type littermates, none of these phenotypes were observed in mice, housed in enriched conditions. By contrast, in the hot-plate test, rota-rod and locomotor activity test a genotype-dependent phenotype was observed in mice housed in enriched, but not in standard conditions. Moreover, the phenotype of CCK(2) receptor-deficient mice established in the hot-plate test and rota-rod was sex-specific. These results suggest that thorough and labour-consuming study of mutation-induced behavioural phenotype is necessary not only in different genetic backgrounds but also the substantial variation of phenotype due to sex- and environment-related factors have to be explored.