Cited by 305Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function

Paradee, W., Melikian, H.E., Rasmussen, D.L., Kenneson, A., Conn, P.J., Warren, S.T.·1999·Neuroscience

DOI 10.1016/s0306-4522(99)00285-7

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Abstract

Fragile X syndrome is an X-linked form of mental retardation resulting from the absence of expression of the fragile X mental retardation 1 gene. The encoded protein is a ribosome-associated, RNA-binding protein thought to play a role in translational regulation of selective messenger RNA transcripts. A knockout mouse has been described that exhibits subtle deficits in spatial learning but normal early-phase long-term potentiation. We expanded these studies by examination of late-phase hippocampal long-term potentiation, the protein synthesis-dependent form of long-term potentiation, in the Fmrl knockout mice. Here, late-phase long-term potentiation was normal, suggesting either that absence of fragile X mental retardation protein has no influence on long-term potentiation or that any influence is too subtle to be detected by this technique. Alternatively, the hippocampus may not be the primary site affected by the absence of this protein. Accordingly, we examined spatial learning in the knockout mice using the hippocampus-dependent Morris water maze. Contrary to earlier reports, near-normal performance was observed. Since the knockout line used in this study has been back-crossed to C57BL/6 for more than 15 generations, whereas the line used in the earlier studies contained a substantial strain 129 contribution, we examined F1 siblings of knockout and 129 crosses. Here, significant but subtle increased swim latencies in reversal trials were observed, in agreement with the previous studies. These data suggest strain differences between C57BL/6 and 129 that influence the Fmrl knockout phenotype. In order to investigate a paradigm less dependent on hippocampal function, the knockout mice were examined using the conditional fear paradigm. Here, the knockout animals displayed significantly less freezing behavior than their wild-type littermates following both contextual and conditional fear stimuli. These data suggest that amygdala disturbances may also be involved in fragile X syndrome.

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Authors: Paradee, W., Melikian, H. E., Rasmussen, D. L., Kenneson, A., Conn, P. J., & Warren, S. T.
Affiliations: Howard Hughes Medical Institute (US)
Emory University (US)
Corresponding author: Warren, S.T.
ORCID: Paradee, W.
Melikian, H.E.
Kenneson, A.
Conn, P.J.
Warren, S.T.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 1999-09
Volume: 94
Issue: 1
Pages: 185-192
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/s0306-4522(99)00285-7
OpenAlex: W2110871941
Cited by: 305
References: 51
Citations by year: 2026: 2 · 2025: 1 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 15 · 2018: 11 · 2017: 17 · 2016: 5 · 2015: 14 · 2014: 19 · 2013: 16 · 2012: 15
FWCI: 4.77
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37 HD20521, P01 HD35576, R37HD020521, P01HD035576)
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: fragile X syndrome, Fmr1 knockout mice, FMRP, amygdala, contextual fear, spatial learning, hippocampal long-term potentiation, strain differences, C57BL/6 mice, 129 mice, freezing behavior, translational regulation
MeSH terms: Amygdala, Animals, Conditioning, Psychological, Electrophysiology, Fear, Female, Fragile X Syndrome, Genotype, Hippocampus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Phenotype, Spatial Behavior, RNA-Binding Proteins, Long-Term Potentiation, Mice, Knockout, Maze Learning, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1

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Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function

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