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Cited by 45Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchNeuroscience and Neuropharmacology Research

Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test

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de Esch, C.E.F., van den Berg, W.E., Buijsen, R.A.M., Jaafar, I.A., Nieuwenhuizen-Bakker, I.M., Gasparini, F., Kushner, S.A., Willemsen, R.·2015·Neurobiology of Disease
DOI 10.1016/j.nbd.2014.12.021
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Abstract

Fragile X syndrome is the most common monogenetic form of intellectual disability and autism. Although the Fmr1 knockout mouse model recapitulates many aspects of the human FXS condition, the establishment of robust social behavioural phenotypes suitable for drug screening has been difficult. Here, we describe a novel social behavioural paradigm, the Automated Tube Test (ATT), for which Fmr1 knockout mice demonstrate a highly reliable and robust phenotype. Fmr1 KO mice show highly dominant behaviour over wild-type littermates in the ATT. Consistent with previous findings, we observed a highly significant, albeit partial, rescue of the altered social behaviour of Fmr1 knockout mice in the ATT, using genetic (mGluR5 deletion) or pharmacological inhibition (mGluR5 antagonist) of mGluR5 signalling independently. Together, our results validate the Automated Tube Test as a robust outcome measure for social behaviour in preclinical research for FXS, and confirm the pathophysiological relevance of mGluR5 signalling. Moreover, our findings highlight the strategy of initiating pharmacological intervention in adulthood as holding significant clinical potential.

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Crossref · 10.1016/j.nbd.2014.12.021

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  • Rescue of these behavioural phenotypes has been difficult to consolidate and to use as a guide for clinical studies.

    “As a result, the rescue of these behavioural phenotypes has been difficult to consolidate and to use as a guide for clinical studies30,49,56,64,65.”

    From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [64]

  • Many classic behavioural phenotypes used as preclinical outcome measures are inconsistently observed in Fmr1-knockout mice.

    “many of the other classic behavioural phenotypes used as outcome measures in preclinical studies are inconsistently observed in Fmr1-KO mice (such as open field, rotarod, elevated plus-maze, marble burying, self-grooming and most social paradigms).”

    From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [64]

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Authors
de Esch, C. E. F., van den Berg, W. E., Buijsen, R. A. M., Jaafar, I. A., Nieuwenhuizen-Bakker, I. M., Gasparini, F., Kushner, S. A., & Willemsen, R.
Affiliations
  • Erasmus MC (NL)
  • Novartis (Switzerland) (CH)
Corresponding author
Willemsen, R.
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2015-03
Volume
75
Pages
31-39
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2014.12.021
OpenAlex
W2072063558
Cited by
45
References
62
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 1 · 2015: 2 · 2014: 1
FWCI
4.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
fragile X syndrome, Fmr1 knockout mice, mGluR5, metabotropic glutamate receptor 5, social behavior, dominance behavior, intellectual disability, autism spectrum disorder, mGluR5 antagonist, drug screening
MeSH terms
Animals, Disease Models, Animal, Fragile X Syndrome, Indoles, Male, Mice, Inbred C57BL, Phenotype, Phosphorylation, Psychological Tests, Psychotropic Drugs, Social Behavior, Synapses, Mice, Knockout, Excitatory Amino Acid Antagonists, MAP Kinase Signaling System, Fragile X Messenger Ribonucleoprotein 1, Receptor, Metabotropic Glutamate 5

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