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Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse
Abstract
Previous studies showed the Fmr1 knockout (KO) mouse to be an excellent animal model for human fragile-X syndrome. The aim of this study was to further characterize the phenotype of these animals. Neuroanatomically, KO male mice were compared to wild-types (littermates) with respect to their sizes of hippocampal intra- and infrapyramidal mossy fiber (IIPMF) terminal fields. Behaviorally, they were tested in four different paradigms, each measuring different aspects of cognitive and emotional behavior: elevated plus maze (anxiety), neutral cage (aggression), open field (exploration), and radial maze (spatial memory). The results showed a diminished ability for radial maze learning associated with smaller sizes of IIPMF terminal fields. In addition, Fmr1 knockout animals exhibited increased locomotor activity, while no differences were found for aggression and anxiety. These data suggest the involvement of FMRP protein in the development of spatial learning and the sprouting of IIPMF terminal fields.
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“Among the behavioral phenotypes displayed in Fmr1 KO are deficits in object recognition memory (including a failure to habituate to objects), and impairment of spatial memory (Mineur et al., 2002).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Mineur et al., 2002
In the citing paper
“Several studies indicate that Fmr1 KO mice are hyperactive and show indications of increased anxiety (Bakker et al., 1994; Mineur et al., 2002; Spencer et al., 2005) and sensory hyperre-sponsiveness, especially to auditory stimuli (Chen and Toth, 2001; Frankland et al., 2004; Nielsen et al., 2002).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Mineur et al., 2002
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“Previous studies indicated that FMRP expression appears principally near synapses following neurotransmitter activation and that FMRP plays an important role in maturation and synaptic plasticity (Comery et al., 1997; Weiler et al., 1997; Weiler and Greenough, 1999; Irwin et al., 2000).”
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Social dysfunction and mental retardation
Pietropaolo, S., Sluyter, F., & Crusio, W. E. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781107360556.010
In Vivo Visualization of Single Axons and Synaptic Remodeling in Normal and Pathological Conditions
Grillo, F. W., Canty, A. J., Bloomfield, P. S., & Paola, V. D. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801393-9.00011-6
Experimental Models for Autism Spectrum Disorder Follow-Up for the Validity
Devi, U., Kumar, V., Gupta, P. S., Dubey, S., Singh, M., Gautam, S., Rawat, J. K., Roy, S., Yadav, R. K., Ansari, M. N., et al. (2016) · Review Journal of Autism and Developmental Disorders · doi:10.1007/s40489-016-0088-7
Walsh, R. M. (2016) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Glycogen Synthase Kinase-3: Abnormalities and Therapeutic Potential in Fragile X Syndrome
Jope, R. S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00013-5
Role of retinoic acid signaling in homeostatic synaptic plasticity
Sarti, F. (2013) · eScholarship (California Digital Library)
Metadata
- Authors
- Mineur, Y. S., Sluyter, F., de Wit, S., Oostra, B. A., & Crusio, W. E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Erasmus University Rotterdam (NL)
- King's College London (GB)
- Corresponding author
- Crusio, Wim E.
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2002-01
- Volume
- 12
- Issue
- 1
- Pages
- 39-46
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- OpenAlex
- W2042310987
- Cited by
- 216
- References
- 56
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 10 · 2017: 12 · 2016: 11 · 2015: 10 · 2014: 21 · 2013: 14 · 2012: 16
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R01 HD 38038, R01HD038038)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Fmr1 knockout mice, fragile X syndrome, FMRP, spatial learning, radial maze, anxiety, aggression, locomotor activity, neuroanatomy, cognitive behavior
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Disease Models, Animal, Exploratory Behavior, Fragile X Syndrome, Hippocampus, Humans, Male, Memory, Mice, Inbred C57BL, Motor Activity, Nerve Tissue Proteins, RNA-Binding Proteins, Mice, Knockout, Maze Learning, Mossy Fibers, Hippocampal, Mice, Fragile X Messenger Ribonucleoprotein 1
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