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Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
Open accessAbstract
Fragile X syndrome arises from blocked expression of the fragile X mental retardation protein (FMRP). Golgi-impregnated mature cerebral cortex from fragile X patients exhibits long, thin, tortuous postsynaptic spines resembling spines observed during normal early neocortical development. Here we describe dendritic spines in Golgi-impregnated cerebral cortex of transgenic fragile X gene ( Fmr1 ) knockout mice that lack expression of the protein. Dendritic spines on apical dendrites of layer V pyramidal cells in occipital cortex of fragile X knockout mice were longer than those in wild-type mice and were often thin and tortuous, paralleling the human syndrome and suggesting that FMRP expression is required for normal spine morphological development. Moreover, spine density along the apical dendrite was greater in the knockout mice, which may reflect impaired developmental organizational processes of synapse stabilization and elimination or pruning.
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“These effects, together with spine elongation, suggests a phenotype of reduced or delayed synapse maturation that is reminiscent of the phenotypes observed in mouse models of fragile X syndrome (Comery et al., 1997; Irwin et al., 2001), Rett syndrome (Armstrong, 2005; Belichenko et al., 2009; Chao et al., 2007), and Angelman syndrome (Dindot et al., 2008; Sato and Stryker, 2010; Yashiro et al., 2”
From Modeling Autism by SHANK Gene Mutations in Mice (2013) · cites this paper as Comery et al., 1997
In the citing paper
“The increased spine length and density observed in human postmortem studies were replicated in Fmr1 KO mice [74, 167–169], although differences were noted dependent on age and brain area.”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [74]
In the citing paper
“Absence of FMRP in both humans and mice results in improper development of dendritic spines on cortical pyramidal neurons (Comery et al., 1997; Irwin et al., 2000; Irwin et al., 2001; Irwin et al., 2002).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Comery et al., 1997
In the citing paper
“In a mouse model of Fragile X syndrome, spines are more numerous, and a higher percentage of them appear immature upon examination of adult fixed tissues (Comery et al., 1997; Irwin et al., 2000).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Comery et al., 1997
In the citing paper
“In a mouse model of Fragile X syndrome, spines are more numerous, and a higher percentage of them appear immature upon examination of adult fixed tissues (Comery et al., 1997; Irwin et al., 2000).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Comery et al., 1997
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Additional file 1 of Fmr1 exon 14 skipping in late embryonic development of the rat forebrain
Corrêa-Velloso, J. C., Linardi, A., Glaser, T., Velloso, F. J., Rivas, M. P., Leite, R. E. P., Grinberg, L. T., Ulrich, H., Akins, M. R., Chiavegatto, S., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19947736
Schmitt, L. M., Li, J., Liu, R., Horn, P. S., Sweeney, J. A., Erickson, C. A., & Pedapati, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26552614
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Metadata
- Authors
- Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., & Greenough, W. T.
- Affiliations
- University of Antwerp (BE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-05-13
- Volume
- 94
- Issue
- 10
- Pages
- 5401-5404
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC24690
- OpenAlex
- W2022959185
- Cited by
- 1,046
- References
- 30
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 28 · 2023: 20 · 2022: 35 · 2021: 24 · 2020: 34 · 2019: 38 · 2018: 35 · 2017: 52 · 2016: 41 · 2015: 45 · 2014: 64 · 2013: 57 · 2012: 43
- FWCI
- 14.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- FRAXA Research Foundation (MH35321)
- John D. and Catherine T. MacArthur Foundation
- National Institute of Mental Health (MH-35321, R01MH035321, R37MH035321)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- fragile X syndrome, FMRP, Fmr1 knockout mice, dendritic spines, dendritic spine morphology, synaptic pruning, synapse stabilization, layer 5 pyramidal neurons, occipital cortex, Golgi impregnation, postsynaptic spines
- MeSH terms
- Animals, Cerebral Cortex, Dendrites, Female, Fragile X Syndrome, Golgi Apparatus, Humans, Mice, Inbred Strains, Occipital Lobe, Pyramidal Cells, Mice, Knockout, Mice
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