Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder

DeLorey, Timothy M.; Sahbaie, Peyman; Hashemi, Ezzat; Homanics, Gregg E.; Clark, J. David

doi:10.1016/j.bbr.2007.09.009

Cited by 207 publications

(165 citation statements)

References 76 publications

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“…Holding associations to a standard of 100% replication would be similar to dismissing the role of a particular mutation after not seeing it in a small case series. Additional support for the common variant approach comes from data indicating that mice with mutations in genes for which association is well established (for example, reelin and Gabrb3) show ASDlike abnormalities 73,74 . Not only should rare and common variant approaches be pursued in parallel, but an integration of the results from both methods will also be necessary.…”

Section: Association Studiesmentioning

confidence: 99%

Advances in autism genetics: on the threshold of a new neurobiology

2008

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Autism is a heterogeneous syndrome defined by impairments in three core domains: social interaction, language and range of interests. Recent work has led to the identification of several autism susceptibility genes and an increased appreciation of the contribution of de novo and inherited copy number variation. Promising strategies are also being applied to identify common genetic risk variants. Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme.Autistic disorder is the most severe end of a group of neurodevelopmental disorders referred to as autism spectrum disorders (ASDs), which share the common feature of dysfunctional reciprocal social interaction. A meta-analysis of ASD prevalence rates suggests that approximately 37 in 10,000 individuals are affected 1 . ASDs encompass several clinically defined conditions (see BOX 1 and the Diagnostic and Statistical Manual of Mental Disorders), pervasive developmental disorder -not otherwise specified and autistic disorder are the most common, whereas Asperger syndrome appears less frequently. Boys are at increased risk for the ASDs, an effect that becomes even more pronounced in so-called high-functioning cases.A chronological overview of research in the ASDs underscores the short history of genetic work in this area as well as the diversity of the methods used. Before the 1970s, autism was not widely appreciated to have a strong biological basis. Instead, various psychodynamic interpretations, including the role of a cold or aloof style of mothering, were invoked as potential causes. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript co-occurrence of chromosomal disorders and rare syndromes with the ASDs were noted 2 . Subsequent twin and family studies provided additional support for a complex genetic aetiology, but these were limited by the lack of uniform diagnostic criteria. The development of validated diagnostic and assessment tools in the early 1990s, most notably the Autism Diagnostic Interview -Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), addressed these concerns and these tools have proven crucial to the advancement of international research into the ASDs. This work, in concert with important technical advances, made it possible to carry out the first candidate gene association studies and resequencing efforts in the late 1990s. Whole-genome linkage studies followed, and were used to identify additional loci of potential interest. Although the application of genome-wide techniques to assess copy number variation (CNV) has only just begun 3-5 , these studies have already identified a large number of potentially important novel candidate loci.Thus, in contrast to the complete absence of any biological understanding of the ASDs as recently as 30 years ago, we now know that defined mutations, genetic syndromes and de novo CNV acco...

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Section: Association Studiesmentioning

confidence: 99%

Advances in autism genetics: on the threshold of a new neurobiology

2008

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“…Social behavior assays have been conducted with many of the mouse models in which imaging studies were conducted. Employing our 3-chambered social approach task, a simple yes-or-no assay for sociability [13], absence of sociability was reported in mice with mutations in genes including Shank3 [15,16], Cntnap2 [17], Pten [18], Tsc1 [19], En2 [20], Gabrb3 [21], Ube3a triplication [22], and oxytocin receptor knockouts [23]. Normal 3-chambered social approach appeared in mice with mutations in genes including oxytocin [24], Shank1 [25], Nlgn2 [26], Ephrin-A [27] and 16p11.2 deletion [28] Variable findings on social approach across laboratories and in mouse lines generated on different genetic backgrounds have been reported for mutations including Fmr1 [29,30], Nlgn3 [31][32][33][34], and Nlgn4 [35,36].…”

Section: Discoveries Of Autism-relevant Behaviors In Mouse Modelsmentioning

confidence: 99%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on highresolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery.

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“…Interestingly, one study showed that the GABRB3 gene was monoallelically expressed in autistic brain samples, whereas it was biallelically expressed in control samples [160], implying altered GABA signaling in ASD. Inactivation of GABRB3, conventionally or conditionally, in mice results in significant impairments in development, and social behaviors, and also causes stereotypical behavior [161][162][163][164].…”

Section: The Gamma-aminobutyric Acid Receptor Subunit Beta-3 (Gabrb3)mentioning

confidence: 99%

The complex genetics in autism spectrum disorders

Hua

Wei

Zhang

2015

Sci. China Life Sci.

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Autism spectrum disorders (ASD) are a pervasive neurodevelopmental disease characterized by deficits in social interaction and nonverbal communication, as well as restricted interests and stereotypical behavior. Genetic changes/heritability is one of the major contributing factors, and hundreds to thousands of causative and susceptible genes, copy number variants (CNVs), linkage regions, and microRNAs have been associated with ASD which clearly indicates that ASD is a complex genetic disorder. Here, we will briefly summarize some of the high-confidence genetic changes in ASD and their possible roles in their pathogenesis.autism spectrum disorders, genetics, causative genes, copy number variants Citation:Hua R, Wei MP, Zhang C. The complex genetics in autism spectrum disorders. Sci China Life Sci, 2015, 58: 933 -945,

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Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder

Abstract: The observed behavioral deficits, especially regarding social behaviors, strengthens the face validity of the gabrb3 gene deficient mouse as being a model of autism spectrum disorder.

Cited by 207 publications

References 76 publications

Advances in autism genetics: on the threshold of a new neurobiology

Advances in autism genetics: on the threshold of a new neurobiology

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

The complex genetics in autism spectrum disorders

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