Audiogenic Seizures Susceptibility in Transgenic Mice with Fragile X Syndrome
Abstract
Purpose To evaluate their susceptibility to audiogenic seizures, five groups of knockout mice with various forms of fragile X genetic involvement [hemizygous males (n = 46), and homozygous (n = 38) and heterozygous females (n = 45), and their normal male (n = 45) and female (n = 52) littermates] were studied. Methods All mouse groups were tested at ages 17, 22, 35, and 45 days. Audiogenic seizure susceptibility was scored, and the analysis of variance was used for the evaluation of the effects of age and genetic condition on seizure severity score (SSS). Results All groups of knockout fragile X mice exhibited SSSs significantly higher than those observed in their wild-type littermates; among knockout mice, hemizygous males and homozygous females showed the highest SSSs. Hemizygous males showed higher SSSs with increasing age, from 17 to 45 days; homozygous females showed a peak at age 22 days, followed by a decrease; finally, heterozygous females had their highest SSSs at age 17 days. Conclusions This study demonstrates that an increased susceptibility to audiogenic seizures is present in fragile X knockout mice at all the ages tested. These results support the validity of this animal model also for epilepsy and seizures in the human fragile X syndrome.
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Fmr1 mutant mice are highly susceptible to seizures and exhibit abnormally high cortical network synchrony during juvenile stages.
“Consistently, Fmr1 mutant mice are highly susceptible to seizures 103 and exhibit abnormally high cortical network synchrony during juvenile stages 104 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [103]
Auditory hypersensitivity is also evident in Fmr1 KO mice, which exhibit increased susceptibility to audiogenic seizures and abnormal auditory startle.
“Auditory hypersensitivity is also evident in Fmr1 knockout (KO) mice, a mouse model of FXS, which exhibit increased susceptibility to audiogenic seizures (Musumeci et al., 2000) and abnormal auditory startle (Frankland et al., 2004).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Musumeci et al., 2000
Cites
Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkert, A. J. M. H., Holden, J. J. A., Fenwick, R. G., Warren, S. T., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90283-5 · Cited by 2,080 · see citing works
Self-citationAbnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5401 · Cited by 1,046 · see citing works
Self-citationAnalysis of neocortex in three males with the Fragile X syndrome
Hinton, V. J., Brown, W. T., Wisniewski, K., & Rudelli, R. D. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320410306 · Cited by 527 · see citing works
Eberhart, D. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.8.1083 · Cited by 390 · see citing works
Adult fragile X syndrome: Clinico-neuropathologic findings
Rudelli, R. D., Brown, W. T., Wisniewski, K., Jenkins, E. C., Laure-Kamionowska, M., Connell, F., & Wisniewski, H. M. (1985) · Acta Neuropathologica · doi:10.1007/bf00687814 · Cited by 362 · see citing works
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Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.004 · Cited by 521 · see citing works
Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice
Michalon, A., Sidorov, M., Ballard, T. M., Ozmen, L., Spooren, W., Wettstein, J. G., Jaeschke, G., Bear, M. F., & Lindemann, L. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.009 · Cited by 489 · see citing works
Clement, J. P., Aceti, M., Creson, T. K., Ozkan, E. D., Shi, Y., Reish, N. J., Almonte, A. G., Miller, B. H., Wiltgen, B. J., Miller, C. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.045 · Cited by 385 · see citing works
Developmental timing and critical windows for the treatment of psychiatric disorders
Marín, O. (2016) · Nature Medicine · doi:10.1038/nm.4225 · Cited by 374 · see citing works
Decreased expression of the GABAA receptor in fragile X syndrome
D'Hulst, C., De Geest, N., Reeve, S. P., Van Dam, D., De Deyn, P. P., Hassan, B. A., & Kooy, R. F. (2006) · Brain Research · doi:10.1016/j.brainres.2006.08.115 · Cited by 318 · see citing works
Circuit level defects in the developing neocortex of fragile X mice
Gonçalves, J. T., Anstey, J. E., Golshani, P., & Portera-Cailliau, C. (2013) · Nature Neuroscience · doi:10.1038/nn.3415 · Cited by 279 · see citing works
Fragile X syndrome: a review of associated medical problems
Kidd, S. A., Lachiewicz, A., Barbouth, D., Blitz, R. K., Delahunty, C., McBrien, D., Visootsak, J., & Berry-Kravis, E. (2014) · Pediatrics · doi:10.1542/peds.2013-4301 · Cited by 255 · see citing works
Modeling fragile X syndrome in the <i>Fmr1</i> knockout mouse
Kazdoba, T. M., Leach, P. T., Silverman, J. L., & Crawley, J. N. (2014) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2014.01024 · Cited by 241 · see citing works
Epilepsy in fragile X syndrome
Berry‐Kravis, E. (2002) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2002.tb00277.x · Cited by 271 · see citing works
A phenotypic and molecular characterization of the <i>fmr1‐tm1Cgr</i> Fragile X mouse
Yan, Q. J., Asafo‐Adjei, P. K., Arnold, H. M., Brown, R. E., & Bauchwitz, R. P. (2004) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2004.00087.x · Cited by 213 · see citing works
Circuit and Plasticity Defects in the Developing Somatosensory Cortex of<i>Fmr1</i>Knock-Out Mice
Bureau, I., Shepherd, G. M. G., & Svoboda, K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1076-08.2008 · Cited by 201 · see citing works
Sinclair, D., Oranje, B., Razak, K. A., Siegel, S. J., & Schmid, S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.029 · Cited by 198 · see citing works
CGG repeat in the FMR1 gene: size matters
Willemsen, R., Levenga, J., & Oostra, B. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01723.x · Cited by 184 · see citing works
Self-citationThe Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00270 · Cited by 170 · see citing works
Altered differentiation of neural stem cells in fragile X syndrome
Castrén, M., Tervonen, T., Kärkkäinen, V., Heinonen, S., Castrén, E., Larsson, K., Bakker, C. E., Oostra, B. A., & Åkerman, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508995102 · Cited by 176 · see citing works
Self-citationGenetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice
Pietropaolo, S., Guilleminot, A., Martin, B., D'Amato, F. R., & Crusio, W. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017073 · Cited by 178 · see citing works
Cortical HCN channels: Function, trafficking and plasticity
Shah, M. M. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.270058 · Cited by 160 · see citing works
Min, W. W., Yuskaitis, C. J., Yan, Q., Sikorski, C., Chen, S., Jope, R. S., & Bauchwitz, R. P. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.09.017 · Cited by 146 · see citing works
Early developmental alterations in GABAergic protein expression in fragile X knockout mice
Adusei, D. C., Pacey, L. K. K., Chen, D., & Hampson, D. R. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.05.002 · Cited by 139 · see citing works
Pacey, L. K. K., Heximer, S. P., & Hampson, D. R. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056127 · Cited by 133 · see citing works
Augmentation of auditory N1 in children with fragile X syndrome.
Castrén, M., Pääkkönen, A., Tarkka, I. M., Ryynänen, M., & Partanen, J. (2003) · Brain Topography · doi:10.1023/a:1022606200636 · Cited by 123 · see citing works
Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody, S. M., Wilson‐Wallis, E. D., Royston, S., Tagliatela, S. M., Naegele, J. R., & Lombroso, P. J. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00781.x · Cited by 108 · see citing works
CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome
Abekhoukh, S., & Bardoni, B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00081 · Cited by 110 · see citing works
Electrocortical changes associated with minocycline treatment in fragile X syndrome
Schneider, A., Leigh, M. J., Adams, P., Nanakul, R., Chechi, T., Olichney, J., Hagerman, R., & Hessl, D. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113494105 · Cited by 108 · see citing works
Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice.
Dansie, L. E., Phommahaxay, K., Okusanya, A. G., Uwadia, J., Huang, M., Rotschafer, S. E., Razak, K. A., Ethell, D. W., & Ethell, I. M. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.058 · Cited by 95 · see citing works
El Bekay, R., Romero‐Zerbo, Y., Decara, J., Sanchez‐Salido, L., Del Arco‐Herrera, I., Rodríguez‐de Fonseca, F., & De Diego‐Otero, Y. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05939.x · Cited by 85 · see citing works
Musumeci, S. A., Calabrese, G., Bonaccorso, C. M., D'Antoni, S., Brouwer, J. R., Bakker, C. E., Elia, M., Ferri, R., Nelson, D. L., Oostra, B. A., et al. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2006.08.007 · Cited by 70 · see citing works
Self-citationGarcia-Pino, E., Gessele, N., & Koch, U. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2310-16.2017 · Cited by 58 · see citing works
Hyperexcitability and homeostasis in fragile X Syndrome.
Liu, X., Kumar, V., Tsai, N.-P., & Auerbach, B. D. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.805929 · Cited by 53 · see citing works
De Rubeis, S., Fernández, E., Buzzi, A., Di Marino, D., & Bagni, C. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-7091-0932-8_23 · Cited by 48 · see citing works
Lovastatin, Not Simvastatin, Corrects Core Phenotypes in the Fragile X Mouse Model
Muscas, M., Louros, S. R., & Osterweil, E. K. (2019) · eneuro · doi:10.1523/eneuro.0097-19.2019 · Cited by 30 · see citing works
Stem cells and modeling of autism spectrum disorders
Freitas, B. C. G., Trujillo, C. A., Carromeu, C., Yusupova, M., Herai, R. H., & Muotri, A. R. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2012.09.017 · Cited by 27 · see citing works
Luque, M. A., Morcuende, S., Torres, B., & Herrero, L. (2024) · The Journal of Physiology · doi:10.1113/jp285244 · Cited by 9 · see citing works
- Authors
- Musumeci, S. A., Bosco, P., Calabrese, G., Bakker, C., De Sarro, G. B., Elia, M., Ferri, R., & Oostra, B. A.
- Affiliations
- University of Reggio Calabria (IT)
- Erasmus University Rotterdam (NL)
- Corresponding author
- Musumeci, Sebastiano A.
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2000-12
- Volume
- 41
- Issue
- 1
- Pages
- 19-23
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W1974810696
- Cited by
- 289
- References
- 5
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 5 · 2017: 16 · 2016: 10 · 2015: 9 · 2014: 17 · 2013: 14 · 2012: 14
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- audiogenic seizures, fragile X syndrome, seizure susceptibility, animal models of epilepsy, hemizygous males, heterozygous females
- MeSH terms
- Acoustic Stimulation, Aging, Analysis of Variance, Animals, Female, Fragile X Syndrome, Heterozygote, Homozygote, Mice, Neurologic Mutants, Mice, Transgenic, Mice, Knockout, Genetic Predisposition to Disease, Epilepsy, Reflex, Mice
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