Mildly impaired water maze performance in maleFmr1 knockout mice
Abstract
Fmr1 knockout mice constitute a putative model of fragile X syndrome, the most common form of heritable mental disability in humans. We have compared the performance of transgenic mice with an Fmr1 knockout with that of normal littermates in hidden- and visible-platform water maze learning, and showed that knockouts exhibit subnormal spatial learning abilities and marginal motor performance deficits. During 12 training trials of the hidden-platform task, escape latency and path length decreased significantly in knockouts and control littermates, and no effect of genotype was found. During four ensuing reversal trials, however, significant differences were found between knockouts and control littermates both in escape latency and path length. During the visible-platform condition, the reversal trials also revealed a difference between knockouts and normal littermates in escape latency, but not in path length. Possibly due to marginal motor incapacity, knockouts swam significantly slower than controls during these latter trials. During both probe trials of the hidden-platform task, knockouts as well as normal littermates spent more time in the target quadrant than in the other quadrants, and percent of time spent in the target quadrant was the same in both groups; swimming velocity was not significantly different between knockouts and normal littermates during these trials. Entries in the target area during the probe trials did show a significant effect of genotype on number of entries. The present results largely confirm and extend our previous findings. Impaired spatial abilities in Fmr1 knockouts might have been due to relatively low response flexibility or high memory interference in Fmr1 knockouts. It remains unclear, however, which brain region or neurochemical system might be involved in these disabilities. We conclude that Fmr1 knockout mice might be a valid model of fragile X mental retardation.
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The behavioral and cognitive deficits of Fmr1 KO mice are actually quite subtle and parallel Fragile X syndrome patients.
“By most accounts Fmr1 KO mice appear to have relatively normal behavior, but research has shown that the behavioral and cognitive deficits of the KO are actually quite subtle and parallel FXS patients (Berry-Kravis et al., 2002; D’Hooge et al., 1997; Paradee et al., 1999; Peier et al., 2000).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as D’Hooge et al., 1997
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- Authors
- D'Hooge, R., Nagels, G., Franck, F., Bakker, C. E., Reyniers, E., Storm, K., Kooy, R. F., Oostra, B. A., Willems, P. J., & De Deyn, P. P.
- Affiliations
- University of Antwerp (BE)
- Erasmus University Rotterdam (NL)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1997-01
- Volume
- 76
- Issue
- 2
- Pages
- 367-376
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2038361969
- Cited by
- 208
- References
- 30
- Citations by year
- 2026: 1 · 2025: 5 · 2023: 9 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 7 · 2014: 12 · 2013: 12 · 2012: 5
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- Fmr1 knockout mice, fragile X syndrome, spatial learning, water maze, reversal learning, response flexibility, memory interference
- MeSH terms
- Animals, Cues, Learning Disabilities, Male, Mice, Inbred C57BL, Reversal Learning, Space Perception, Swimming, Mice, Knockout, Maze Learning, Mice
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