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 working 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.

Deficiency of the CYLD Impairs Fear Memory of Mice and Disrupts Neuronal Activity and Synaptic Transmission in the Basolateral Amygdala

“…Recent studies in which researchers performed whole-exome sequencing in FTD patients also showed that patients carrying Cyld mutations suffer severe memory impairment (Dobson-Stone et al, 2020;Tábuas-Pereira et al, 2020). In addition, numerous studies have revealed the role of other DUBs (USP2, USP6, USP14, USP46, and UCHL1) in promoting learning and memory (recognition memory, fear memory, and spatial memory) in rodents (Imai et al, 2013;Jarome et al, 2013;Zhang et al, 2014;Zeng et al, 2019;Srikanta et al, 2021). These reports indicate that DUBs including CYLD are involved in fear memory modulation.…”

“…According to recent reports, Cyld is a causative gene for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (Dobson-Stone et al, 2020), and patients carrying Cyld variants show severe memory loss (Tábuas-Pereira et al, 2020). Several studies have shed light on the role of deubiquitinases (DUBs), such as ubiquitin-specific protease (USP) and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), in the modulation of synaptic plasticity and memory processes (Imai et al, 2013;Jarome et al, 2013;Zhang et al, 2014;Zeng et al, 2019;Srikanta et al, 2021). Nevertheless, the functions of CYLD in neuronal activity and neural circuits remain largely unknown.…”

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.…”

In Cerebellar Atrophy of 12-Month-Old ATM-Null Mice, Transcriptome Upregulations Concern Most Neurotransmission and Neuropeptide Pathways, While Downregulations Affect Prominently Itpr1, Usp2 and Non-Coding RNA

“…The ATM-interacting MRN complex responsible for DNA damage signalling did not show any changed mRNA levels, but the NBS1 stabilising factor Usp2 mRNA displayed a downregulation of similar effect size and significance as Atm mRNA [86]. USP2-null mice show impaired motor coordination and balance [174], so its deficiency in an ATM-null cerebellum might contribute to ataxia pathogenesis. This deubiquitinase is also known as a regulator of circadian clock components [175], and indeed several USP2 effectors also showed deficient transcript levels, such as Cry1 and Cry2.…”