Document text
Principal Investigator: MATTHEW N RASBAND
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $400,000
Funding agency: National Institute of Mental Health
New Abstract: The causes of complex neuropsychiatric disorders including schizophrenia, bipolar disorder, and autism remain poorly understood. Importantly, many neuropsychiatric disorders are highly heritable, indicating the underlying cause is genetic rather than environmental. Large genome-wide association studies (GWAS) have begun to reveal specific genes associated with these disorders. Among these, ANK3 (the gene coding for AnkyrinG (AnkG)) is potentially associated with bipolar disorder, schizophrenia, and autism. However, how ANK3 variants contribute to these disorders remains unknown. Importantly a loss-of-function ANK3 splice variant containing a novel exon (termed BDex) found only in oligodendrocytes may be protective against bipolar disease. We previously found AnkG in paranodes of myelinating oligodendrocytes, where it functions in the timely assembly of paranodal junctions during early development. However, the function of oligodendroglial AnkG in older mice remains unknown. We will determine the function of AnkG in oligodendrocytes, and more specifically the function of BDex. We will define the precise location of BDex-containing AnkG in oligodendrocytes. We will use loss-of-function and gain-of-function mouse models to investigate the role of oligodendroglial ANK3 variants in the brain. We will examine node and paranode structure, myelin, myelinated axon physiology, and behavior. Together, these studies will begin to uncover the role of oligodendroglial AnkG and BDex AnkG, and may reveal insights into the molecular pathophysiology of ANK3-associated neuropsychiatric disorders.
Terms: <12-20 years old><21+ years old><ANK3><ANK3 gene><ASD><Adhesion Molecule><Adolescence><Adult><Adult Human><Affect><Age Months><Amino Acids><Ankyrin 3><Ankyrin-G><Autism><Autistic Disorder><Axon><Behavior><Bio-Informatics><Bioinformatics><Biological><Bipolar Affective Psychosis><Bipolar Disorder><Brain><Brain Nervous System><Causality><Cell Adhesion Molecule Gene><Cell Adhesion Molecules><Cell Communication and Signaling><Cell Junctions><Cell Signaling><Code><Coding System><Complex><Defect><Development><Diagnosis><Disease><Disorder><Dysfunction><Early Infantile Autism><Encephalon><Etiology><Exons><Functional disorder><GWA study><GWAS><Gene Expression><Genes><Genetic><Genotype><Heritability><Infantile Autism><Intercellular Junctions><Intracellular Communication and Signaling><Isoforms><K channel><KO mice><Kanner's Syndrome><Knock-out Mice><Knockout Mice><Link><Lipids><Location><Manic-Depressive Psychosis><Mice><Mice Mammals><Modeling><Modification><Molecular><Moods><Murine><Mus><Myelin><Nerve Cells><Nerve Conduction><Nerve Unit><Neural Cell><Neural Conduction><Neurocyte><Neurons><Null Mouse><Oligodendrocytes><Oligodendrocytus><Oligodendroglia><Oligodendroglia Cell><Pathogenesis><Persons><Physiology><Physiopathology><Play><Potassium Channel><Potassium Ion Channels><Protein Isoforms><RNA Splicing><Ranvier's Nodes><Reporting><Reproducibility><Risk><Role><Scaffolding Protein><Schizophrenia><Schizophrenic Disorders><Signal Transduction><Signal Transduction Systems><Signaling><Site><Splicing><Structure><Symptoms><Transcript><Treatment Efficacy><United States><Variant><Variation><adolescence (12-20)><adulthood><aged mice><aged mouse><aminoacid><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><biologic><biological signal transduction><bipolar affective disorder><bipolar disease><bipolar illness><bipolar mood disorder><causation><cell adhesion protein><conditional knock-out><conditional knockout><dementia praecox><developmental><disease causation><elderly mice><gain of function><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><hypomania><hypomanic><insight><intervention efficacy><loss of function><manic depressive disorder><manic depressive illness><mouse model><murine model><myelination><neurofascin><neuronal><neuropsychiatric disease><neuropsychiatric disorder><novel><old mice><overexpress><overexpression><pathophysiology><schizophrenic><social role><substantia alba><therapeutic efficacy><therapy efficacy><white matter><whole genome association analysis><whole genome association studies><whole genome association study>