scholarly journals Overview of current mouse models of autism and strategies for their development using CRISPR/Cas9 technology

2018 ◽  
Vol 112 (1) ◽  
pp. 19
Author(s):  
Anja DOMADENIK
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Genome Engineering ◽  
New Technologies ◽  
Current Knowledge ◽  
Autism Spectrum ◽  
Phenotypic Traits ◽  
Knock Out ◽  
Sgrna Design ◽  
Spectrum Disorders

<p>Autism spectrum disorders (ASD) are a group of highly heterogenous neurological disorders that are believed to have strong genetic component. Due to the limited use of approaches of functional genomics in human medicine, creating adequate animal models for the study of complex human diseases shows great potential. There are several already established mouse models of autism that offer insight into single phenotypic traits, although causes for its complex phenotype have not yet been fully understood. Development of new technologies, such as CRISPR/Cas9, represent great capability for targeted genome engineering and establishment of new animal models. This article provides an up to date overview of current knowledge in the area of autism genomics and describes the potential of CRISPR/Cas9 technology for the establishment of new mouse models, representing sgRNA design as one of the initial steps in planning a CRISPR/Cas9 single knock-out experiment. In addition, it offers an overview of current approaches to behavioural studies, explaining how relevant animal models could be developed.</p>

scholarly journals The Role of Bacterial-Derived Aromatic Amino Acids Metabolites Relevant in Autism Spectrum Disorders: A Comprehensive Review

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuanpeng Zheng ◽  
Marie K. Bek ◽  
Naika Z. Prince ◽  
Lucia N. Peralta Marzal ◽  
Johan Garssen ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Animal Models ◽  
Current Knowledge ◽  
Aromatic Amino Acids ◽  
Nutritional Intervention ◽  
Autism Spectrum ◽  
Acid Fermentation ◽  
Microglial Phagocytosis ◽  
Spectrum Disorders

In recent years, the idea of the gut microbiota being involved in the pathogenesis of autism spectrum disorders (ASD) has attracted attention through numerous studies. Many of these studies report microbial dysregulation in the gut and feces of autistic patients and in ASD animal models. The host microbiota plays a large role in metabolism of ingested foods, and through the production of a range of metabolites it may be involved in neurodevelopmental disorders such as ASD. Two specific microbiota-derived host metabolites, p-cresol sulfate and 4-ethylphenyl sulfate, have been associated with ASD in both patients and animal models. These metabolites originate from bacterially produced p-cresol and 4-ethylphenol, respectively. p-Cresol and 4-ethylphenol are produced through aromatic amino acid fermentation by a range of commensal bacteria, most notably bacteria from the Clostridioides genus, which are among the dysregulated bacteria frequently detected in ASD patients. Once produced, these metabolites are suggested to enter the bloodstream, pass the blood–brain-barrier and affect microglial cells in the central nervous system, possibly affecting processes like neuroinflammation and microglial phagocytosis. This review describes the current knowledge of microbial dysbiosis in ASD and elaborates on the relevance and synthesis pathways of two specific ASD-associated metabolites that may form a link between the microbiota and the brain in autism. While the two discussed metabolites are promising candidates for biomarkers and (nutritional) intervention targets, more research into the role of these metabolites in ASD is required to causally connect these metabolites to ASD pathophysiology.

scholarly journals Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model

2019 ◽  
Vol 20 (9) ◽  
pp. 2134 ◽  
Author(s):  
Ann Katrin Sauer ◽  
Juergen Bockmann ◽  
Konrad Steinestel ◽  
Tobias M. Boeckers ◽  
Andreas M. Grabrucker
Keyword(s):  
Autism Spectrum Disorders ◽  
Inflammatory Responses ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Intestinal Morphology ◽  
Microbiota Composition ◽  
Knock Out ◽  
E Coli ◽  
The Central Nervous System ◽  
Spectrum Disorders

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by deficits in social interaction and communication, and repetitive behaviors. In addition, co-morbidities such as gastro-intestinal problems have frequently been reported. Mutations and deletion of proteins of the SH3 and multiple ankyrin repeat domains (SHANK) gene-family were identified in patients with ASD, and Shank knock-out mouse models display autism-like phenotypes. SHANK3 proteins are not only expressed in the central nervous system (CNS). Here, we show expression in gastrointestinal (GI) epithelium and report a significantly different GI morphology in Shank3 knock-out (KO) mice. Further, we detected a significantly altered microbiota composition measured in feces of Shank3 KO mice that may contribute to inflammatory responses affecting brain development. In line with this, we found higher E. coli lipopolysaccharide levels in liver samples of Shank3 KO mice, and detected an increase in Interleukin-6 and activated astrocytes in Shank3 KO mice. We conclude that apart from its well-known role in the CNS, SHANK3 plays a specific role in the GI tract that may contribute to the ASD phenotype by extracerebral mechanisms.

Genetic and non-genetic animal models for autism spectrum disorders (ASD)

2016 ◽  
Vol 64 ◽  
pp. 116-140 ◽  
Author(s):  
Zivanit Ergaz ◽  
Liza Weinstein-Fudim ◽  
Asher Ornoy
Keyword(s):  
Autism Spectrum Disorders ◽  
Animal Models ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Sleep, brain development, and autism spectrum disorders: Insights from animal models

2020 ◽  
Vol 98 (6) ◽  
pp. 1137-1149 ◽  
Author(s):  
Taylor Wintler ◽  
Hannah Schoch ◽  
Marcos G. Frank ◽  
Lucia Peixoto
Keyword(s):  
Autism Spectrum Disorders ◽  
Animal Models ◽  
Brain Development ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Resveratrol in Autism Spectrum Disorders: Behavioral and Molecular Effects

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 188 ◽  
Author(s):  
Michele Malaguarnera ◽  
Haroon Khan ◽  
Omar Cauli
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Autism Spectrum ◽  
Immune Alteration ◽  
Stress Markers ◽  
Behavioral Abnormalities ◽  
Spectrum Disorders ◽  
Core Symptoms ◽  
And Oxidative Stress

Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxiety and cognitive function. The molecular mechanisms by which RSV restores or improves behavioral abnormalities in animal models encompass both normalization of central and peripheral immune alteration and oxidative stress markers and new molecular mechanisms such as expression of cortical gamma-amino butyric acid neurons, certain type of miRNAs that regulate spine growth. One randomized, placebo-controlled clinical trial (RCT) suggested that RSV add-on risperidone therapy improves comorbid hyperactivity/non-compliance, whereas no effects where seen in core symptoms of ASD No RCTs about the effect of RSV as monotherapy have been performed and the results from preclinical studies encourage its feasibility. Further clinical trials should also identify those ASD patients with immune alterations and/or with increased oxidative stress markers that would likely benefit from RSV administration.

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