Understanding fragile X syndrome: insights from animal models

Bakker, Cathy; Oostra, Ben A.

doi:10.1159/000072845

Cited by 81 publications

(49 citation statements)

References 149 publications

(204 reference statements)

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“…Animal models for fragile X have been developed in mice (Bakker, 1994;Gao, 2002;Bakker and Oostra, 2003;Kooy, 2003), Drosophila (Wan et al, 2000), and zebrafish (van 't Padje et al, 2005). An FMRP ortholog has been identified in zebrafish and found to be expressed in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Four independent studies showed that LTP in the CA1 region of the hippocampus was unaltered in FMR1 KO mice (Godfraind et al, 1996;Paradee et al, 1999;Li et al, 2002), despite reported deficits in hippocampal-dependent spatial memory and contextual fear memory (D'Hooge et al, 1997;Paradee et al, 1999;Van Dam et al, 2000;Bakker and Oostra, 2003) (Table 1). Another study reported a reduction in LTP within the somatosensory cortex of FMR1 KO mice (Li et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Normal locomotor activity, nociceptive responses, and anxiety-like behaviors in FMR1 KO mice Previous studies have reported alterations in locomotor activity and anxiety levels as a result of the deletion of FMR1 (Peier et al, 2000;Nielsen et al, 2002;Bakker and Oostra, 2003). Because hyperactivity may interfere with the correct recording of the behavioral freezing response, we placed FMR1 WT and KO mice in an open field and recorded their locomotor activity.…”

Section: Impaired Trace Fear Memory In Fmr1 Ko Micementioning

confidence: 99%

See 2 more Smart Citations

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Zhao¹,

Toyoda²,

Ko³

et al. 2005

J. Neurosci.

267

272

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Trace fear memory requires the activity of the anterior cingulate cortex (ACC) and is sensitive to attention-distracting stimuli. Fragile X syndrome is the most common form of mental retardation with many patients exhibiting attention deficits. Previous studies in fragile X mental retardation 1 (FMR1) knock-out (KO) mice, a mouse model for fragile X, focused mainly on hippocampal-dependent plasticity and spatial memory. We demonstrate that FMR1 knock-out mice show a defect in trace fear memory without changes in locomotion, anxiety, and pain sensitivity. Whole-cell path-clamp recordings in the ACC show that long-term potentiation (LTP) was completely abolished. A similar decrease in LTP was found in the lateral amygdala, another structure implicated in fear memory. No significant changes were found in basal synaptic transmission. This suggests that synaptic plasticity in the ACC and amygdala of FMR1 KO mice plays an important role in the expression of behavioral phenotypes similar to the symptoms of fragile X syndrome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Impaired Trace Fear Memory In Fmr1 Ko Micementioning

confidence: 99%

See 1 more Smart Citation

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Zhao¹,

Toyoda²,

Ko³

et al. 2005

J. Neurosci.

267

272

View full text Add to dashboard Cite

show abstract

“…FXS resulted from the expansion of a CGG trinucleotide repeat in the 5' untranslated region of the fragile X mental retardation 1 (fmr1) gene. Dendritic spine morphology between Fmr1 KO and wild type mouse [112]. Overabundance of immature dendritic spine (bulbous head and a thin neck) is expressed in Fmr1 KO mouse [63,65].…”

Section: Synergistic Effect Of Melatonin On Synaptic Plasticity In Aumentioning

confidence: 99%

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

Won

Jin

Lee

et al. 2017

Preprint

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Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

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“…The fragile X knockout mouse, a validated model for the disorder, showed no visible dysmorphism. [6][7][8] More recently, anatomical phenotyping in the mouse model using MRI imaging found no significant craniofacial abnormalities. 9 Studies in zebrafish show conflicting results.…”

Section: Introductionmentioning

confidence: 99%

Craniofacial characteristics of fragile X syndrome in mouse and man

Heulens

Suttie²,

Постнов

et al. 2012

Eur J Hum Genet

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For a disorder as common as fragile X syndrome, the most common hereditary form of cognitive impairment, the facial features are relatively ill defined. An elongated face and prominent ears are the most commonly accepted dysmorphic hallmarks. We analysed 3D facial photographs of 51 males and 15 females with full FMR1 mutations and 9 females with a premutation using dense-surface modelling techniques and a new technique that forms a directed graph with normalized face shapes as nodes and edges linking those with closest dysmorphism. In addition to reconfirming known features, we confirmed the occurrence of some at an earlier age than previously recorded. We also identified as yet unrecorded facial characteristics such as reduced facial depth, hypoplasticity of the nasal bone-cartilage interface and narrow mid-facial width exaggerating ear prominence. As no consistent craniofacial abnormalities had been reported in animal models, we analysed micro-CT images of the fragile X mouse model. Results indicated altered dimensions in the mandible and both outer and inner skull, with the latter potentially reflecting differences in neuroanatomy. We extrapolated the mouse results to face shape differences of the human fragile X face.

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Understanding fragile X syndrome: insights from animal models

Cited by 81 publications

References 149 publications

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

Craniofacial characteristics of fragile X syndrome in mouse and man

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