Genetics and Neurodevelopmental Disorders

Hippocampal gamma-band oscillopathy in a mouse model of Fragile X Syndrome

This study investigates gamma oscillations in FMR1 KO mice and finds altered power and synchronicity in response to specific agonists, suggesting disrupted signaling pathways in FXS.

Zbtb16 regulates social cognitive behaviors and neocortical development.

This study shows that Zbtb16 deletion in mice causes ASD and SCZ-like behaviors and neocortical developmental defects, with associated transcriptomic changes.

Spatially coordinated heterochromatinization of distal short tandem repeats in fragile X syndrome

The paper shows that in fragile X syndrome, long-range heterochromatinization of distal synaptic genes with STR instability is reversible by overexpression of a pre-mutation-length CGG tract.

KMT2D haploinsufficiency in Kabuki Syndrome disrupts neuronal function through transcriptional and chromatin rewiring independent of H3K4-monomethylation

This study investigates how KMT2D mutations in Kabuki Syndrome disrupt neuronal function through chromatin and transcriptional changes, independent of H3K4me1.

AAV-delivery of diacylglycerol kinase kappa achieves long-term rescue of Fmr1-KO mouse model deficits of fragile X syndrome

AAV-delivered FMRP-independent DGKk corrects brain lipid homeostasis and behavioral deficits in Fmr1-KO mice.

Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice

This study examines synaptic imbalances and homeostatic plasticity disruption in ASD-associated Chd8 haploinsufficient mice, revealing altered excitatory and inhibitory transmission in cortical circuits.

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

The paper identifies de novo PRKAR1B variants in six individuals with neurodevelopmental disorder, autism, apraxia, and reduced pain sensitivity.

Neuroanatomy and Behaviour in Mice with a Haploinsufficiency of AT-Rich Interactive Domain 1B (ARID1B) Throughout Development

This study investigates the effects of Arid1b haploinsufficiency in mice, revealing sex-dependent neuroanatomical and behavioral phenotypes associated with neurodevelopmental disorders.

Complete loss of CASK causes severe ataxia through cerebellar degeneration in human and mouse

This study shows that complete loss of CASK causes cerebellar degeneration in humans and mice, leading to severe ataxia and encephalopathy, while heterozygous loss results in less severe, non-progressive pathology due to X-chromosome inactivation.

Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

This study shows that Brpf1 deficiency in GABAergic interneurons reduces inhibitory neurotransmission and alters Map2k7 expression.

Autism-linked Cullin3 germline haploinsufficiency impacts cytoskeletal dynamics and cortical neurogenesis through RhoA signaling

This study shows that Cul3 haploinsufficiency in mice causes social and cognitive deficits, cortical volume reduction, and cytoskeletal defects, which are rescued by RhoA inhibition.

fmr1 mutation interacts with sensory experience to alter the early development of behavior and sensory coding in zebrafish

This study shows that fmr1 mutation in zebrafish affects early behavioral and sensory coding development, which can be mitigated by altering the sensory environment.

Abnormal AMPAR-mediated synaptic plasticity, cognitive and autistic-like behaviors in a missense Fmr1 mutant mouse model of Fragile X syndrome

This study investigates a missense Fmr1 mutation in mice, showing increased spine density, synaptic defects, and cognitive deficits linked to Fragile X syndrome.

The enhancement of activity rescues the establishment of Mecp2 null neuronal phenotypes

This study shows that enhancing neuronal activity rescues developmental defects in Mecp2 null neurons, improving their maturation and extending lifespan in a mouse model of Rett syndrome.

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

The paper identifies RFX3, RFX4, and RFX7 mutations as causes of neurodevelopmental disorders including autism, ADHD, and intellectual disability, and links these genes to ASD risk genes through bioinformatic analysis.

Neuronal non-CG methylation is an essential target for MeCP2 function

This study shows that MeCP2's binding to non-CG methylation, specifically mCAC trinucleotides, is critical for normal brain function, as demonstrated by severe Rett syndrome-like phenotypes in mice with a modified MeCP2 domain.

Comparing synaptic proteomes across seven mouse models for autism reveals molecular subtypes and deficits in Rho GTPase signaling

The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction

This study shows that KDM5 is essential for synaptic structure and function at the Drosophila neuromuscular junction through both demethylase-dependent and independent mechanisms.

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

The paper identifies mutation-specific pathophysiological mechanisms in SATB1 variants causing distinct neurodevelopmental disorders.

Deleting Mecp2 from the entire cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice

This study shows that deleting Mecp2 from the entire cerebellum, but not from individual cell types, causes a delay in motor learning in mice.

Deconstruction of the retrosplenial granular cortex for social behavior in the mouse model of fragile X syndrome

The paper identifies reduced social-related neuronal activity in the retrosplenial granular cortex (RSG) of Fmr1-KO mice, leading to social novelty deficits and suggests RSG manipulation as a potential therapeutic strategy.

Novel CHD8 genomic targets identified in fetal mouse brain by in vivo Targeted DamID

This study identifies novel CHD8 genomic targets in fetal mouse brain using in vivo Targeted DamID, revealing binding sites related to neurodevelopment and autism-relevant biology.

Increased cortical volume without increased neuron number in heterozygous Chd8 mutant mouse cortex

The paper investigates whether increased cortical volume in Chd8 mutant mice is due to increased neuron number or soma size, finding no increase in neuron number but increased volume.

In vivo CGG repeat RNA binding protein capture identifies RAN translation modifiers and suppressors of repeat toxicity.

The paper identifies RAN translation modifiers and suppressors of repeat toxicity by studying CGG repeat RNA-binding proteins in vivo.

A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions

This paper introduces a CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency that mirrors human phenotypes, including cognitive impairments and epilepsy, and identifies synaptic transmission deficits.

SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice

This study identifies a SENP1 mutation in mice that causes core autistic-like symptoms by disrupting the SENP1-FMRP axis in the retrosplenial agranular cortex.

Reduced complexity of brain and behavior due to MeCP2 disruption and excessive inhibition

This study investigates how MeCP2 disruption in rats leads to excessive inhibition, increased neuronal synchrony, and stereotyped motor behavior, suggesting an E/I imbalance underlies motor dysfunction in Rett syndrome.

Methyl-CpG2-binding protein 2 mediates overlapping mechanisms across brain disorders.

The paper identifies MeCP2 target genes associated with multiple brain disorders and shows they share common molecular mechanisms in neuronal transmission, immunity, and development.

Atypical Neocortical Development in the Cited2 Conditional Knockout Leads to Behavioral Deficits Associated with Neurodevelopmental Disorders

This study shows that Cited2 conditional knockout in the forebrain leads to neocortical abnormalities and specific behavioral deficits resembling neurodevelopmental disorders.

Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys

This study uses in vivo CRISPR/Cas9 to edit MECP2 in adolescent rhesus monkeys, resulting in autistic-like behaviors.