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 (abl2^-/-) mice to explore its impact on sensory/motor functions and emotion-related behaviors. Our findings show that abl2^-/- 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 abl2^-/- mice compared to WT mice. Furthermore, in the tail suspension test, abl2^-/- 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 abl2^-/- and WT mice, suggesting the absence of working memory deficits and impulsivity in abl2^-/- mice. Proteomic analysis of the hippocampus in abl2^-/- 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 abl2^-/- compared to WT mice, and intraperitoneal treatment of GABA receptor agonist Gaboxadol normalized anxiety/depression-related behaviors of abl2^-/- 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.