SAT-397 Behavioral Dynamics of Zebrafish Model for Selenoprotein Deficiency Using Gigapixel Microscopy

Abstract Disclosure: F. Marelli: None. L. Persani: None. Zebrafish is a valuable model for elucidating internal human processes through behavioral arrays. Investigating zebrafish locomotion provides insights into neural and sensory processing, while motion tracking offers quantifiable measures of health, stress, and cognitive responses. This study focuses on zebrafish mutants for the SECIS-binding protein 2 (sbp2Q333X/Q333X) gene, which is critical for incorporating selenocysteine into the active centers of selenoproteins (SPs). In humans, biallelic SBP2 mutations lead to a systemic deficiency in SPs activity, manifesting as a multisystem disorder characterized by abnormal thyroid hormone metabolism, muscular dystrophy, intellectual disability, photosensitivity, neural hearing loss, and aorthopathy.The behavior of sbp2Q333X/Q333X mutant larvae and control zebrafish was evaluated using the Multi-Camera Array Microscope (MCAM, Ramona Optics), a high-resolution imaging system equipped with 48 optical sensors arranged in a rectangular grid, capturing nearly 700 megapixels per frame. Convolutional neural networks enabled precise tracking of eight key anatomical points (snout, eyes, fish center, and four tail positions), facilitating comprehensive analysis of startle responses. Metrics such as distance traveled (DT), velocity (V), and tail angle (TA) were quantified in response to visual (light flash) and mechanical (vibration) stimuli.At five days post-fertilization, sbp2Q333X/Q333X mutants exhibited reduced spontaneous exploration but increased swimming distances and velocities during optomotor and thigmotaxis stimuli, compared to controls. Additionally, mutants showed an anxiety-related ‘zig-zag’ swimming patterns, in contrast with the linear trajectories observed in controls.These findings suggest that sbp2Q333X/Q333X mutants exhibit stress-induced escape behavior, potentially linked to deficits in specific SPs, such as antioxidant enzymes. Further analyses are underway to elucidate the mechanisms driving these behavioral changes. Presentation: Saturday, July 12, 2025