Srgap3⁻/⁻ mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes
Robert Waltereit1, Uwe Leimer, Oliver von Bohlen Und Halbach
1Department of Molecular Biology, Central Institute of Mental Health and Heidelberg University, Mannheim, Germany.
Summary
Mutations in the SRGAP3 gene cause neurodevelopmental issues. Srgap3-knockout mice displayed brain abnormalities and behavioral changes, suggesting SRGAP3
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- SRGAP3 gene mutations are linked to intellectual disability.
- SRGAP3 and related genes are implicated as risk factors for schizophrenia.
- SRGAP3 influences cytoskeletal dynamics via RAC1, crucial for brain development and synaptic plasticity.
Purpose of the Study:
- To investigate the role of SRGAP3 in brain development.
- To characterize the neuroanatomical and behavioral consequences of SRGAP3 loss-of-function.
Main Methods:
- Generation and analysis of Srgap3-knockout mice.
- Neuroanatomical examination of brain structures.
- Behavioral testing, including spontaneous alternation, social interaction, and prepulse inhibition.
- Assessment of RAC1 activity.
Main Results:
- Srgap3-knockout mice exhibited hydrocephalus, enlarged ventricles, white matter tracts, and dendritic spines.
- Increased basal RAC1 activity was observed.
- Mice showed impaired social behavior, spontaneous alternation, and tics, with sex-specific differences in locomotor activity and methylphenidate response.
- Prepulse inhibition was impaired in females.
Conclusions:
- SRGAP3 is essential for normal neurodevelopment.
- Loss of SRGAP3 leads to significant neuroanatomical and behavioral phenotypes.
- These findings suggest a role for SRGAP3 mutations in various neurodevelopmental disorders, including schizophrenia.
