- Title Information
- Title
- Phenotyping the ΔIg3-MuSK Mouse Model Using Automated Continuous Behavior Monitoring
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Wang, Jenny Y H
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Fallon, Justin
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Andrade, Arturo
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Department of Molecular Biology, Cell Biology and Biochemistry
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2025
- Physical Description
- Extent
- , None p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2025
- Genre (aat)
- theses
- Abstract
- The MuSK-BMP signaling pathway has been implicated in neuromotor and cognitive regulation, and adult hippocampal neurogenesis, yet its behavioral consequences remain insufficiently understood. To selectively investigate the behavioral consequences of disrupting MuSK-BMP signaling in vivo, the current study employs Automated Continuous Behavior Monitoring (ACBM) to characterize the ΔIg3-MuSK mouse model, which lacks the Ig3 domain required for BMP co-receptor function. ACBM is a computer vision-based machine learning model that enables high-resolution, sensitive, and unbiased quantification of nine defined behaviors across five days in individually housed mice. ΔIg3-MuSK and wild-type mice of both sexes were recorded at five months of age and their behavior was analyzed across zeitgeber time.
Our findings revealed previously undetected, time of darkness-specificity and sexually dimorphic behavioral phenotypes associated with MuSK-BMP signaling disruption. The ΔIg3-MuSK males exhibited early dark hypoactivity, characterized by reductions in neuromotor (walk, rear) and ingestion (drink, eat-by-hand) behaviors. ΔIg3-MuSK females displayed a similar pattern of reduced neuromotor (walk) and exploratory (sniff) behaviors during early dark hours. However, the ΔIg3-MuSK females showed striking spikes in neuromotor (hang) and ingestion (drink, eat) behaviors during late dark hours, which were absent in males. Other sexually dimorphic behaviors observed were sustained elevation in groom in males and reduction in sniff in females throughout the entire dark period. Comparative analysis with 5xFAD, an Alzheimer's disease mouse model, highlights divergent patterns: whereas ΔIg3-MuSK demonstrated hypoactivity in neuromotor behaviors and sustained elevation in groom, 5xFAD mice showed reciprocal hyperactivity in neuromotor (hang, walk, rear) behaviors and sustained reduction in groom, suggesting model-specific behavioral signatures.
Our data suggest that the loss of MuSK-Ig3-mediated BMP signaling in ΔIg3-MuSK mice may modulate sex-specific neural circuits governing self-care, foraging, and stress-related behaviors. These findings establish the power of ACBM for detecting subtle, temporally defined, and long-term behavioral phenotypes in the ΔIg3-MuSK model, with implications for understanding neuromotor function, mood regulation, and neurodegenerative disease mechanisms by providing sensitive and reproducible behavioral readouts.
- Subject
- Topic
- Adult Neurogenesis
- Subject
- Topic
- Automated Continuous Behavioral Monitoring
- Subject
- Topic
- Mouse behavior
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/02032663")
- Topic
- Deep learning (Machine learning)
- Subject
- Topic
- MuSK-BMP
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20250707