Wfs1-deficient mice display impaired behavioural adaptation in stressful environment.

Wfs1-deficient mice were generated by disrupting the 8th exon of Wfs1 gene. Reproduction rates of homozygous Wfs1-deficient mice were slightly below the expected values, they displayed intolerance to glucose and overall lower body weight. The present behavioural study was performed in female Wfs1-deficient mice due to their milder metabolic disturbances. Non-fasting blood glucose levels did not differ between homozygous Wfs1-deficient mice and wild-type littermates. While there was no difference in baseline plasma corticosterone, exposure to stress induced a nearly three-fold elevation of corticosterone in Wfs1-deficient mice in relation to wild-type littermates. Wfs1-deficient mice did not display obvious shortcomings in sensory and motor functioning as exemplified by intact responses in conditioned learning paradigms and rota-rod test. Locomotor activity of Wfs1-deficient mice was significantly lower only in brightly lit environment. Short-term isolation had a significant anxiogenic-like effect on the behaviour of Wfs1-deficient mice in dark/light exploration test. Lower exploratory activity of Wfs1-deficient mice in the plus-maze was antagonised by pre-treatment with diazepam (1 mg/kg), a GABA(A) receptor agonist. Wfs1-deficient mice displayed increased anxiety-like behaviour in hyponeophagia test. The locomotor stimulatory effects of amphetamine (2.5-7.5 mg/kg) and apomorphine (3 mg/kg) were significantly attenuated and facilitated, respectively, in Wfs1-deficient mice. There were no differences between Wfs1-deficient mice and wild-types in forced swimming behaviour and conditioned fear responses. Subtle impairments in reversal learning were apparent in Wfs1-deficient mice in the Morris water maze. Altogether, the present study demonstrates impaired behavioural adaptation of Wfs1-deficient mice in stress-inducing situations. It is likely that Wfs1 protein plays a major role in the behavioural adaptation mechanisms to novel and stressful environments.

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.