|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
This evidence supports Shank3-ko NSCs as a reliable in vitro disease model and suggests the rescue of glial cells as a therapeutic strategy to prevent neuronal degeneration in ASD.
|
31773410 |
2020 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Mutations in ASD-associated SHANK3 in mice (Shank3B<sup>-/-</sup>) result in the accelerated maturation of corticostriatal circuits during the second and third postnatal weeks.
|
31722214 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Shank3, an abundant excitatory postsynaptic scaffolding protein, has been associated with multiple brain disorders, including autism spectrum disorders (ASD) and Phelan-McDermid syndrome (PMS).
|
31649512 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Here we used two highly trusted ASD mouse models (male Shank3-deficient [Shank3<sup>+/ΔC</sup> ] mice modeling the monogenic etiology of ASD, and inbred BTBR mice [both male and female] modeling the idiopathic and highly polygenic pathology for ASD) to evaluate the level of motivation to engage in a social interaction.
|
31602784 |
2020 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors.
|
31398341 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Therefore, in CA3 pyramidal neurons of Shank3-mutant mice, glutamatergic but not GABAergic activity is affected at early developmental stages, hence reflecting the heterogeneity of mechanisms underlying the pathogenesis of ASD.
|
31354805 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations.
|
31319798 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Here we generated and characterized a <i>Shank3</i> knock-in mouse line carrying the Q321R mutation (<i>Shank3</i><sup>Q321R</sup> mice) identified in a human individual with ASD that affects the ankyrin repeat region (ARR) domain of the Shank3 protein.
|
31275112 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome.
|
31189958 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
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.
|
31052177 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Intriguingly, all ASD Shank3 mutations impaired mGluR-dependent LTD without altering NMDAR-dependent LTD. Our data show that the specific perturbation in mGluR-dependent synaptic plasticity occurs in neurons expressing ASD-associated Shank3 mutations, which may underpin synaptic dysfunction and subsequent behavioral deficits in ASD.
|
30868621 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
To assess whether deletion of Shank3 in mice results in ASD-like behavior, we conducted a battery of behavioral experiments to characterize Shank3B<sup>-/-</sup> mice, including repetitive grooming behavior tests, three-chamber tests and resident-intruder tests.
|
30809159 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations.
|
30763456 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
These results, obtained through the analysis of de novo SHANK3 mutations in the patients' genomic background, provide further support for the presence of synaptic abnormalities in a subset of patients with ASD.
|
30643170 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family.
|
30629339 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Introduction of this human ASD mutation into mice resulted in a small subset of phenotypes seen previously in constitutive Shank3 knockout mice, including increased allogrooming, increased social dominance, and reduced pup USV.
|
30610205 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
De novo mutations (DNMs) of SHANK3 were subsequently identified in patients with several neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia (SCZ), a Rett syndrome-like phenotype, and intellectual disability (ID).
|
30537371 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Given the zinc sensitivity of young neurons and its dependence on Shank2 and Shank3, genetic mutations and/or environmental insults during early development could impair synaptic maturation and circuit formation that underlie ASD etiology.
|
30524232 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
As ASD-associated SHANK3 mutations retain responsiveness to zinc, here we investigated how increasing levels of dietary zinc could alter behavioral and synaptic deficits that occur with ASD.
|
30405356 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
In order to more closely evaluate the contribution of SHANK3 to neurodevelopmental expression of ASD, a knockout mouse model with a mutation in the PDZ domain was developed.
|
30385192 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Whether the impairments in associative learning observed in ASD relate to SHANK3 insufficiency restricted to the reward system is still an open question.
|
30364266 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
Biomarker
|
disease |
BEFREE |
Shank3 is an excitatory postsynaptic scaffolding protein implicated in multiple brain disorders, including autism spectrum disorders (ASD) and Phelan-McDermid syndrome (PMS).
|
30356810 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Although a number of mouse models with Shank3 mutations have been valuable for investigating the pathogenesis of ASD, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model ASD and to translate experimental therapeutics to the clinic.
|
30329048 |
2019 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder.
|
30317697 |
2018 |
|
Autism Spectrum Disorders
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Male mice with a deletion of the PDZ domain of Shank3 (Shank3B KO) were previously shown to display ASD-like behavioral phenotypes with reported self-injurious repetitive grooming and aberrant social interactions.
|
30134148 |
2019 |