Neurodevelopmental disorders are common, debilitating disorders including autism, intellectual disability, and perhaps even schizophrenia. Recent genetic findings have identified mutations in multiple genes in various cellular pathways as genetic causes of neurodevelopmental disorders including autism spectrum disorders, intellectual disability, and others. This proposal will characterize novel and innovative genetic mouse models to delineate the function of these genes in the brain. Specifically, the proposal will focus on two genes implicated in either 16p11.2 deletion or autism, both of which are predicted to be involved in overlapping intra- neuronal signaling pathways and regulation of neuronal and synaptic function/development based on preliminary findings. In addition to identifying the neuronal function of these genes in the brain, these studies will identify potential therapeutic strategies for treatment of genetic forms of autism and intellectual disability and possibly other neurodevelopmental disorders. Progress to date is substantial in that two novel mutant mouse models relevant for neurodevelopmental disorders have been established and preliminary characterization of synaptic function, neuronal development, neuronal biochemistry, and neuronal morphology among other aspects of brain function has begun. Unbiased proteomic/transcriptomic approaches to identifying additional, novel downstream targets of these gene products in mammalian brain will generate new hypotheses anticipated to lead to additional potential therapeutic strategies.

Public Health Relevance

It is critical to better understand genetic causes of human neurodevelopmental disorders such as autism, intellectual disability, and schizophrenia and to use animal models of such causes to identify potential treatments. This 5-year R01 proposal capitalizes on significant progress in creating and characterizing two novel animal models of neurodevelopmental disorders that will allow us to rapidly advance this field. Extensive characterization of these new models will allow for a complete understanding of how genetic mutations in these genes alter brain function and behavior, allowing for future studies aimed at correcting altered brain function in the hope of treating behavioral symptoms in both the models and in patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH113948-01A1
Application #
9990339
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Winsky, Lois M
Project Start
2020-03-10
Project End
2025-01-31
Budget Start
2020-03-10
Budget End
2021-01-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Neurosciences
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294