scholarly journals Fmr1KO Mice as a Possible Model of Autistic Features

2006 ◽  
Vol 6 ◽  
pp. 1164-1176 ◽  
Author(s):  
Maude Bernardet ◽  
Wim E. Crusio
Keyword(s):  
Social Interactions ◽  
Fragile X Syndrome ◽  
Developmental Disorders ◽  
Developmental Disorder ◽  
Fragile X ◽  
Cellular Level ◽  
Restricted Interests ◽  
Autism Research ◽  
Hereditary Component ◽  
Autistic Symptoms

Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level and how they come about remains sketchy. To improve this situation, autism research is in need of valid animal models. However, despite a strong hereditary component, attempts to identify genes have generally failed, suggesting that many different genes are involved. As a high proportion of patients suffering from the Fragile X Syndrome show many autistic symptoms, a mouse model of this disorder could potentially also serve as a model for autism. TheFmr1KO mouse is a valid model of the Fragile X Syndrome and many data on behavioral and sensory-motor characteristics of this model have been gathered. We present here an assessment of autistic features in this candidate model. We conclude thatFmr1KO mice display several autistic-like features, but more work is needed to validate this model.

scholarly journals Autism Spectrum Disorder in Children and Adolescents With Fragile X Syndrome: Within-Syndrome Differences and Age-Related Changes

2010 ◽  
Vol 115 (4) ◽  
pp. 307-326 ◽  
Author(s):  
Andrea McDuffie ◽  
Leonard Abbeduto ◽  
Pamela Lewis ◽  
Sara Kover ◽  
Jee-Seon Kim ◽  
...  
Keyword(s):  
Social Interaction ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Repetitive Behaviors ◽  
Effect Sizes ◽  
Autism Symptoms ◽  
Restricted Interests ◽  
Age Related ◽  
Reciprocal Social Interaction ◽  
Age Related Changes

Abstract The Autism Diagnostic Interview-Revised (ADI-R) was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents who had fragile X syndrome, with and without autism. After controlling for nonverbal IQ, we found statistically significant between-group differences for lifetime and current autism symptoms for the Communication and Restricted Interests/Repetitive Behaviors domains, but not the Reciprocal Social Interaction domain. Effect sizes for differences in Reciprocal Social Interaction also were smaller than effect sizes for the other domains, with one exception. Overall, severity of autism symptoms improved with age for all participants, with the least improvement noted for Restricted Interests and Repetitive Behaviors. FMRP did not account for unique variance in autism symptoms over and above nonverbal IQ.

scholarly journals Fragile X syndrome screening in Chinese children with unknown intellectual developmental disorder

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Xiaoli Chen ◽  
Jingmin Wang ◽  
Hua Xie ◽  
Wenjuan Zhou ◽  
Ye Wu ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Developmental Disorder ◽  
Fragile X ◽  
Chinese Children ◽  
Intellectual Developmental Disorder

scholarly journals Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome

2021 ◽  
Vol 22 (1) ◽  
pp. 410
Author(s):  
Byung Geun Ha ◽  
Jung-Yoon Heo ◽  
Yu-Jin Jang ◽  
Tae-Shin Park ◽  
Ju-Yeon Choi ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Fragile X Syndrome ◽  
Extracellular Vesicles ◽  
Mitochondrial Membrane ◽  
Developmental Disorders ◽  
Fragile X ◽  
Autism Spectrum ◽  
Mitochondrial Transcription Factor ◽  
Spectrum Disorders ◽  
Vimentin Intermediate Filament

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).

Fragile X Syndrome: Recognition in Young Children

PEDIATRICS ◽  
1989 ◽  
Vol 83 (4) ◽  
pp. 547-552
Author(s):  
Aaron Simko ◽  
Lusia Hornstein ◽  
Shirley Soukup ◽  
Nancy Bagamery
Keyword(s):  
Mental Retardation ◽  
Family History ◽  
Young Children ◽  
Fragile X Syndrome ◽  
Developmental Disorders ◽  
Motor Coordination ◽  
Fragile X ◽  
Nasal Bridge ◽  
History Of ◽  
Physical Findings

In recent years, a number of articles have appeared in the literature concerning the fragile X syndrome; however, in few cases was the diagnosis of the syndrome in young children discussed. A review of 20 children younger than 7½ years of age who had the fragile x syndrome seen at the Cincinnati Center of Developmental Disorders was undertaken in an attempt to establish guidelines that would aid the practicing physician in determining which children should have a chromosomal analysis. All children were developmentally delayed; 95% had speech delays. Short attention span with hyperactivity, temper tantrums, mouthing of objects persisting at an age beyond when it would be expected, autistic behaviors, and poor gross motor coordination were seen in 50% or more of the children. Mental retardation was present in the family history of 65%, and 90% had a family history of at least one of the following mental retardation, learning disabilities, or hyperactivity. The most common physical findings were long and/or wide and/or protruding ears, prominent jaw and/or long face, high arched palate, and a flattened nasal bridge. The fragile x syndrome can be recognized by noting key aspects of the behavioral and family histories as well as the physical findings.

The Influence of Environmental and Genetic Factors on Behavior Problems and Autistic Symptoms in Boys and Girls With Fragile X Syndrome

PEDIATRICS ◽  
2001 ◽  
Vol 108 (5) ◽  
pp. e88-e88 ◽  
Author(s):  
D. Hessl ◽  
J. Dyer-Friedman ◽  
B. Glaser ◽  
J. Wisbeck ◽  
R. G. Barajas ◽  
...  
Keyword(s):  
Behavior Problems ◽  
Fragile X Syndrome ◽  
Genetic Factors ◽  
Fragile X ◽  
Autistic Symptoms

scholarly journals Laboratorial diagnosis of fragile-X syndrome: experience in a sample of individuals with pervasive developmental disorders

2005 ◽  
Vol 63 (3a) ◽  
pp. 564-570 ◽  
Author(s):  
Carlos Eduardo Steiner ◽  
Marilisa Mantovani Guerreiro ◽  
Antonia Paula Marques-de-Faria ◽  
Iscia Lopes-Cendes
Keyword(s):  
Fragile X Syndrome ◽  
Behavioral Problems ◽  
Pervasive Developmental Disorders ◽  
Developmental Disorders ◽  
Southern Blotting ◽  
Fragile Site ◽  
Fragile X ◽  
Molecular Study ◽  
Southern Blotting Analysis ◽  
Blotting Analysis

Fragile X syndrome is a frequent genetic disease associated to developmental disorders, including learning disability, mental retardation, behavioral problems and pervasive developmental disorders (autism and related conditions). We studied a sample of 82 individuals (69 males and 13 females) presenting with pervasive developmental disorders using three techniques for the diagnosis of fragile X syndrome (FXS). Cytogenetic analysis detected the fragile site in four males, but only one showed a consistent positive rate. Molecular study based on the PCR technique was inconclusive for most females (92.3%), which where latter submitted to Southern blotting analysis, and for one male (1.4%), excluding the FRAXA mutation in the remaining male individuals (98.6%). Molecular tests using the Southern blotting technique confirmed only one positive case (1.2%) in a male subject. These results showed that Southern blotting analysis of the FRAXA mutation has the best sensitivity and specificity for the diagnosis of FXS but also validated the PCR technique as a confinable screening test.

scholarly journals Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome

2020 ◽  
Vol 21 (23) ◽  
pp. 9327
Author(s):  
Qi Ding ◽  
Fan Zhang ◽  
Yue Feng ◽  
Hongbing Wang
Keyword(s):  
Protein Synthesis ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Genetic Disorder ◽  
Cellular Level ◽  
Neuronal Signaling ◽  
Object Location Memory ◽  
Extracellular Signal ◽  
Elevated Protein ◽  
Phosphoinositide 3 Kinase

Fragile X syndrome (FXS) is a leading genetic disorder of intellectual disability caused by the loss of the functional fragile X mental retardation protein (FMRP). To date, there is no efficacious mechanism-based medication for FXS. With regard to potential disease mechanisms in FXS, it is widely accepted that the lack of FMRP causes elevated protein synthesis and deregulation of neuronal signaling. Abnormal enhancement of the ERK½ (extracellular signal-regulated kinase ½) and PI3K-Akt (Phosphoinositide 3 kinase-protein kinase B) signaling pathways has been identified in both FXS patients and FXS mouse models. In this study, we show that carbamazepine, which is an FDA-approved drug and has been mainly used to treat seizure and neuropathic pain, corrects cognitive deficits including passive avoidance and object location memory in FXS mice. Carbamazepine also rescues hyper locomotion and social deficits. At the cellular level, carbamazepine dampens the elevated level of ERK½ and Akt signaling as well as protein synthesis in FXS mouse neurons. Together, these results advocate repurposing carbamazepine for FXS treatment.

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