MAPPING SEX‑SPECIFIC SENSORY–PSYCHOMOTOR DYSREGULATION IN A NEURONAL GROWTH REGULATOR 1 (NEGR1) KNOCKOUT MICE

Understanding sensory and psychomotor phenotypes remains underexplored, yet it is critically important for advancing psychiatric disorder research, especially regarding sex‑specific differences. Animal models are essential for revealing sex differences in sensory–psychomotor outcomes and their underlying mechanisms. Neuronal Growth Regulator 1 (NEGR1), a member of the IgLON family of neuronal cell adhesion molecules, plays a role in neuronal connectivity and brain development. In recent years, large-scale genetic studies from neuropsychiatric consortia have robustly associated NEGR1 with neuropsychiatric disorders and body-weight-related phenotypes. Negr1 Knockout (Negr1^-/-) mice exhibit neuropsychological deficits in mood, social functioning, and cognition. Here, we aim to investigate sensory-psychomotor processing in male and female adult Negr1^-/- mice. The assessment includes anatomical examination of Negr1 mRNA probes during embryonic development, behavioral examination across sensory-motor domains, biochemical, and immunohistochemical analyses. Result reveals Negr1 expression across developing cranial nerves and peripheral tissues, suggesting a potential role in shaping sensorimotor pathways. We also identified sex specific differences in balance, somatosensory, and sensorimotor processing. Gait abnormalities indicative of psychomotor slowing, including reduced velocity, cadence, and stride length, support psychomotor disruption in this mouse model. Ongoing work using immunostaining and biochemical analysis uncovers the mechanisms linking Negr1 to these domains. Altogether, our findings position NEGR1 as a regulator of sensory–psychomotor development and uncover sex-specific differences, underscoring the need to study both male and female mice to reveal mechanisms underlying neuropsychiatric risk. This work aligns with the RDoC matrix proposal to incorporate sensory-motor domains that are widely implicated but underrepresented in neuropsychiatric research.