A5070998316- Williams Syndrome Research
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Animal Nutrition and Physiology
- Autism Spectrum Disorder Research
- Primate Behavior and Ecology
- RNA regulation and disease
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Animal Genetics and Reproduction
- Early Childhood Education and Development
Washington University in St. Louis
2019-2023
Within eukaryotic cells, translation is regulated independent of transcription, enabling nuanced, localized, and rapid responses to stimuli. Neurons respond transcriptionally translationally synaptic activity. Although transcriptional are documented in astrocytes, here we test whether astrocytes have programmed translational responses. We show that seizure activity rapidly changes the transcripts on astrocyte ribosomes, some predicted be downstream BDNF signaling. In acute slices, quantify...
Abstract Gtf2ird1 and Gtf2i are two transcription factors (TFs) among the 28 genes deleted in Williams syndrome, prior mouse models of each TF show behavioral phenotypes. Here we identify their genomic binding sites developing brain test for additive effects mutation on behavior. GTF2IRD1 targets were enriched transcriptional chromatin regulators mediators ubiquitination. GTF2I signal transduction proteins, including phosphorylation WNT. Both TFs highly at promoters, strongly overlap CTCF...
The Social Approach Task is commonly used to identify sociability deficits when modeling liability factors for autism spectrum disorder (ASD) in mice. It was developed expand upon existing assays examine distinct aspects of social behavior rodents and has become a standard component mouse ASD-relevant phenotyping pipelines. However, there variability the statistical analysis interpretation results from this task. A common analytical approach conduct within-group comparisons only, then...
Abstract Williams syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety specific phobias along with perturbed motor function. caused by microdeletion 26–28 genes on chromosome 7, GTF2IRD1 , which encodes transcription factor suggested to play role in the profile syndrome. Duplications full region also lead frequent autism diagnosis, language delay. Thus, appear regulate motivation...
Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, oxytocin (OT) dysregulation hypothesized to be involved as some studies have shown elevated blood OT altered receptor expression patients. A "Complete Deletion" (CD) mouse, modeling hemizygous deletion Syndrome, recapitulates many present humans. These CD mice also exhibit...
Abstract Gene expression requires two steps – transcription and translation which can be regulated independently to allow nuanced, localized, rapid responses cellular stimuli. Neurons are known respond transcriptionally translationally bursts of brain activity, a transcriptional response this activation has also been recently characterized in astrocytes. However, the extent astrocytes is unknown. We tested hypothesis that have programmed translational by characterizing change transcript...
Abstract The Social Approach Task is commonly used to identify sociability deficits when modeling liability factors for autism spectrum disorder (ASD) in mice. It was developed expand upon assays available examine distinct aspects of social behavior rodents and has become a standard component mouse ASD-relevant phenotyping pipelines. However, there variability the statistical analysis interpretation results from this task. A common analytical approach conduct within-group comparisons only,...
Abstract Gtf2ird1 and Gtf2i may mediate aspects of the cognitive behavioral phenotypes Williams Syndrome (WS) – a microdeletion syndrome encompassing these transcription factors (TFs). Knockout mouse models each TF show phenotypes. Here we identify their genomic binding sites in developing brain, test for additive effects mutation on behavior. Both TFs target constrained chromatin modifier synaptic protein genes, including significant number ASD genes. They bind promoters, strongly overlap...
Abstract Williams Syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety specific phobias along with perturbed motor function. caused by microdeletion 26-28 genes on chromosome 7, GTF2IRD1 , which encodes transcription factor suggested to play role in the profile Syndrome. Duplications full region also lead frequent autism diagnosis, phobias, language delay. Thus, appear regulate motivation...
ABSTRACT Williams Syndrome is caused by a deletion of 26-28 genes on chromosome 7q11.23. Patients with this disorder have distinct behavioral phenotypes including learning deficits, anxiety, increased phobias, and hypersociability. Some studies also suggest elevated blood oxytocin altered receptor expression, dysregulation hypothesized to be involved in the underlying mechanisms driving subset these phenotypes. A ‘Complete Deletion’ mouse, modeling hemizygous critical region Syndrome,...