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Wfs1-deficient mice display impaired behavioural adaptation in stressful environment

Behavioural Brain Research
Publication Date
DOI: 10.1016/j.bbr.2008.11.007
  • Wfs1
  • Wolfram Syndrome
  • Transgenic Mice
  • Homologous Recombination
  • Stress
  • Corticosterone
  • Anxiety
  • Behavioural Adaptation
  • Stress-Induced Analgesia
  • Motility Box
  • Amphetamine
  • Apomorphine
  • Mesolimbic System
  • Dopamine
  • Exploratory Behaviour
  • Diazepam
  • Rota-Rod
  • Hyponeophagia
  • Fear Conditioning
  • Morris Water Maze
  • Active Avoidance
  • Forced Swimming Test
  • Elevated Plus-Maze Test
  • Light-Dark Exploration Test
  • Biology


Abstract 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.

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