Wfs1-deficient mice display impaired behavioural adaptation in stressful environment

Luuk, Hendrik; Plaas, Mario; Raud, Sirli; Innos, Jürgen; Sütt, Silva; Lasner, Helena; Abramov, Urho; Kurrikoff, Kaido; Kõks, Sulev; Vasar, Eero

doi:10.1016/j.bbr.2008.11.007

Cited by 65 publications

(60 citation statements)

References 55 publications

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“…In the study by Luuk et al [13], it was revealed that amphetamine (an indirect acting dopamine agonist) dose-dependently increased the locomotor activity in wild-type, heterozygous Wfs1 and homozygous Wfs1 mutant animals, while in homozygous Wfs1 mutant mice, this effect was statistically significantly less expressed. Vice versa, in the same study, the apomorphine, a direct D 1 -D 2 receptor agonist, had an opposite effect on locomotor activity, and this result allows speculating on the impairment of the dopamine release rather than the alterations in dopamine receptor-related mechanisms of Wfs1 KO mice.…”

Section: Introductionmentioning

confidence: 95%

“…Like in humans, in mutant mice models with Wfs1 gene knocked out (Wfs1 KO), evidence has been collected that the wfs1 protein is an important link between the endocrine and CNS systems [9,29]. The growth of the Wfs1 KO mice is retarded, they weigh less, and they have serious carbohydrate metabolism dysregulation as compared with the wild-type littermates [13]. In addition, the Wfs1 KO animals are emotionally and motivationally deviated, and although not well documented, they may express some cognitive deficit as well.…”

Section: Introductionmentioning

confidence: 97%

“…In addition, the Wfs1 KO animals are emotionally and motivationally deviated, and although not well documented, they may express some cognitive deficit as well. In particular, the mental deficiency of the Wfs1 KO mice seems to be associated with stressful events and situations [13,18].…”

Section: Introductionmentioning

confidence: 99%

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Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge

et al. 2010

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Loss of function of the Wfs1 gene causes Wolfram syndrome, a rare multisystem degenerative disorder. Mutant mice with targeted Wfs1 gene disruption (Wfs1 KO) display morphological and behavioral impairments that are not well understood. The present study aimed to investigate the striatal dopamine output of wild-type, heterozygous, and homozygous Wfs1 null-mutant mice using in vivo microdialysis technique. The baseline dopamine output in striatum was similar in all three animal groups. The application of 100 mM [K+]-rich modified Ringer solution caused in homozygous Wfs1 mutant mice an increase of dopamine output by 400%, while in wild-type and heterozygous animals, the increase of the dopamine output yielded up to 1,200%. In sum, the homozygous Wfs1 mutant mice (AUC₀₋₃ = 0.212 nM/μl h) show significantly decreased striatal dopamine output in response to high-concentration [K+] challenge as compared with wild-type or heterozygous Wfs1 mutant conspecifics (AUC₀₋₃ = 0.427 and 0.505 nM/μl h, respectively). This could explain at least some of the behavioral alterations in Wfs1 mutant mice.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

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Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge

et al. 2010

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“…Therefore, we hypothesize that signaling downstream of the insulin receptor (IR/PI3K/Akt/GSK3 pathway) is compromised as a result of the inactivation of the Wfs1 gene. The Akt pathway has been shown to play a central role in the action of psychostimulant drugs [2][3][4] and Wfs1 mice have a blunted response to amphetamine [32], further supporting the hypothesis that the Akt pathway might be down-regulated in Wfs1 KO mice. The reduced response to amphetamine might also be explained by a reduced dopamine release in Wfs1 KO animals as K + -stimulated striatal DA efflux has been found to be lower in Wfs1 KO mice than in wild-type animals [35].…”

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confidence: 94%

Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin

et al. 2011

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Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. The aim of the present study was to evaluate whether acute valproic acid is able to interfere with glucose intolerance in two different diabetes models: The first model was a Wfs1 mutant mouse with an elevated ER stress response and the second model a streptozocin-induced diabetic mouse. VLP (300 mg/kg, i.p.) was administered to Wfs1 knockout (KO) mice and glucose tolerance test was performed 15 min later. VLP did not have an effect on the course of the glucose tolerance test in wild-type mice, while it did normalize the glucose intolerance in Wfs1 knockout mice. Acute valproic acid also lowered the blood glucose levels in streptozocin-treated mice and potentiated the effect of insulin in these mice. Thus, acute valproic acid is effective in lowering blood glucose levels possibly by potentiating insulin action in both Wfs1 KO mice and in streptozocin-induced type 1 diabetic mice.

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“…In all trials, mice were allowed to swim until 70 s (maximum latency) had elapsed. Starting the following day, trials were performed each day for five consecutive days (Morris, 1984;Luuk et al, 2009). …”

Section: Spatial Learning and Behavioral Studiesmentioning

confidence: 99%

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

Fang

Wang

et al. 2011

J. Zhejiang Univ. Sci. B

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An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze, hematoxylin and eosin (H&E) staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118, P=0.086). Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.

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Wfs1-deficient mice display impaired behavioural adaptation in stressful environment

Cited by 65 publications

References 55 publications

Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge

Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge

Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

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