Cacna1c deficiency in forebrain glutamatergic neurons alters behavior and hippocampal plasticity in female mice.

CACNA1C, coding for the α1 subunit of L-type voltage-gated calcium channel (LTCC) Ca1.2, has been associated with multiple psychiatric disorders. Clinical studies have revealed alterations in behavior as well as in brain structure and function in CACNA1C risk allele carriers.

Development of sex- and genotype-specific behavioral phenotypes in a mouse model for neurodevelopmental disorders.

Individuals with a -related neurodevelopmental disorder, also termed Phelan-McDermid syndrome or abbreviated as PMS, exhibit significant global developmental delay, language impairment, and muscular hypotonia. Also common are repetitive behaviors and altered social interactions, in line with a diagnosis of autism spectrum disorders. This study investigated the developmental aspect of autism-related behaviors and other phenotypes in a -transgenic mouse model.

Elevation of SHANK3 Levels by Antisense Oligonucleotides Directed Against the 3'-UTR of the Human mRNA.

SHANK3 is a member of the SHANK family of scaffolding proteins that localize to the postsynaptic density of excitatory synapses. Mutations within the gene or haploinsufficiency is thought to be one of the major causes for Phelan-McDermid Syndrome (PMDS) that is characterized by a broad spectrum of autism-related behavioral alterations. Several approaches have already been proposed to elevate SHANK3 protein levels in PMDS patients like transcriptional activation or inhibition of SHANK3 degradation.

SHANK3 deficiency leads to myelin defects in the central and peripheral nervous system.

Mutations or deletions of the SHANK3 gene are causative for Phelan-McDermid syndrome (PMDS), a syndromic form of autism spectrum disorders (ASDs). We analyzed Shank3Δ11(-/-) mice and organoids from PMDS individuals to study effects on myelin. SHANK3 was found to be expressed in oligodendrocytes and Schwann cells, and MRI analysis of Shank3Δ11(-/-) mice revealed a reduced volume of the corpus callosum as seen in PMDS patients.

Comparison of SHANK3 deficiency in animal models: phenotypes, treatment strategies, and translational implications.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition, which is characterized by clinical heterogeneity and high heritability. Core symptoms of ASD include deficits in social communication and interaction, as well as restricted, repetitive patterns of behavior, interests, or activities. Many genes have been identified that are associated with an increased risk for ASD.

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression-A Case Report.

Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation.

FUS Mislocalization and Vulnerability to DNA Damage in ALS Patients Derived hiPSCs and Aging Motoneurons.

Mutations within the gene (Fused in Sarcoma) are known to cause Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease affecting upper and lower motoneurons. The gene codes for a multifunctional RNA/DNA-binding protein that is primarily localized in the nucleus and is involved in cellular processes such as splicing, translation, mRNA transport and DNA damage response. In this study, we analyzed pathophysiological alterations associated with ALS related FUS mutations (mFUS) in human induced pluripotent stem cells (hiPSCs) and hiPSC derived motoneurons.

The Shank3 Interaction Partner ProSAPiP1 Regulates Postsynaptic SPAR Levels and the Maturation of Dendritic Spines in Hippocampal Neurons.

The postsynaptic density or PSD is a submembranous compartment containing a wide array of proteins that contribute to both morphology and function of excitatory glutamatergic synapses. In this study, we have analyzed functional aspects of the Fezzin ProSAP-interacting protein 1 (ProSAPiP1), an interaction partner of the well-known PSD proteins Shank3 and SPAR. Using lentiviral-mediated overexpression and knockdown of ProSAPiP1, we found that this protein is dispensable for the formation of both pre- and postsynaptic specializations per se.