Behavioral phenotyping of mice lacking the deubiquitinase USP2

Abstract

Ubiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested. To address this, we ran a battery of behavioral tests on Usp2 KO mice. Firstly, we confirmed our prior findings of increased daily activity and reduced activity fragmentation in Usp2 KO mice. Further, mice lacking USP2 showed impaired motor coordination and equilibrium, a decrease in anxiety-like behavior, a deficit in short-term recognition memory and in sensorimotor gating. On the other hand, no effects of Usp2 gene deletion were found on spatial memory. Hence, our data uncover the implication of USP2 in different behaviors and expands the range of the known functions of this deubiquitinase.

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner

“…Open field Sentra gray boxes were used to measure recognition memory (Şık et al, 2003). The test was performed as previously described (Srikanta et al, 2021) between ZT2 and ZT8 in dim light. On Day 1 of testing, mice were habituated to the empty open-field boxes for 10 min.…”

USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes

“…For example, two groups reported that Usp2 KO mice were more active when they were subjected to a wheel running test [ 86 , 87 ], whereas another group showed that the circadian free-running period and overall locomotor activity of the Usp2 KO mice were not altered [ 90 ]. More recently, a preprint reported that Usp2 KO mice exhibited an increased and more continuous active period compared to control mice [ 127 ]. Usp2 KO mice also perform poorly in rotarod tests, novel object recognition tests, and acoustic startle reflex tests, thereby revealing defects in motor coordination, short-term recognition, and sensorimotor gating, respectively [ 127 ].…”

“…More recently, a preprint reported that Usp2 KO mice exhibited an increased and more continuous active period compared to control mice [ 127 ]. Usp2 KO mice also perform poorly in rotarod tests, novel object recognition tests, and acoustic startle reflex tests, thereby revealing defects in motor coordination, short-term recognition, and sensorimotor gating, respectively [ 127 ]. In addition, plus maze tests and novelty-suppressed feeding tests showed that the Usp2 KO mice have decreased anxiety-like behavior [ 127 ].…”

“…Usp2 KO mice also perform poorly in rotarod tests, novel object recognition tests, and acoustic startle reflex tests, thereby revealing defects in motor coordination, short-term recognition, and sensorimotor gating, respectively [ 127 ]. In addition, plus maze tests and novelty-suppressed feeding tests showed that the Usp2 KO mice have decreased anxiety-like behavior [ 127 ]. The same study did not find any significant differences in appetite or spatial memory formation in Usp2 KO mice, indicating that the roles of USP2 in the central nervous system are relatively specialized [ 127 ].…”

“…In addition, plus maze tests and novelty-suppressed feeding tests showed that the Usp2 KO mice have decreased anxiety-like behavior [ 127 ]. The same study did not find any significant differences in appetite or spatial memory formation in Usp2 KO mice, indicating that the roles of USP2 in the central nervous system are relatively specialized [ 127 ]. Future research may clarify other regulatory roles of USP2 in the brain, and may also uncover the signaling events underlying these phenomena.…”