Impact of Abl2/Arg Deficiency on Anxiety and Depressive Behaviors in mice.

Abl2/Arg (ABL-related gene) is a member of the Abelson family of nonreceptor tyrosine kinases, known for its role in tumor progression, metastasis, tissue injury responses, inflammation, neural degeneration, and other diseases. In this study, we developed Abl2/Arg knockout (arg-/- ) mice to explore its impact on sensory/motor functions and emotion-related behaviors. Our findings show that arg-/- mice exhibit normal growth and phenotypic characteristics, closely resembling their wild-type (WT) counterparts. Behavioral tests, including the elevated plus maze, marble-burying behavior test, and open field test, indicated pronounced anxiety-like behaviors in arg-/- mice compared to WT mice. Furthermore, in the tail suspension test, arg-/- mice showed a significant decrease in mobility time, suggesting depressive-like behavior. Conversely, in the Y-maze and cliff avoidance reaction tests, no notable differences were observed between arg-/- and WT mice, suggesting the absence of working memory deficits and impulsivity in arg-/- mice. Proteomic analysis of the hippocampus in arg-/- mice highlighted significant alterations in proteins related to anxiety and depression, especially those associated with the GABAergic synapse in inhibitory neurotransmission. The expression of Gabbr2 was significantly reduced in the hippocampus of arg-/- compared to WT mice, and intraperitoneal treatment of GABA receptor agonist Gaboxadol normalized anxiety/depression-related behaviors of arg-/- mice. These findings underscore the potential role of Abl2/Arg in influencing anxiety and depressive-like behaviors, thereby contributing valuable insights into its broader physiological and pathological functions.