RecQ helicase family
proteins play vital roles in maintaining
genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five
RecQ helicases: RECQL1,
Bloom syndrome (BLM),
Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ
proteins is associated with
genetic disorders,
tumorigenesis,
premature aging, and neurodegeneration. The biochemical and biological roles of
RecQ helicases are rather well established, however, there is no systematic study comparing the behavioral changes among various RecQ-deficient mice including consequences of exposure to DNA damage. Here, we investigated the effects of ionizing irradiation (IR) on three RecQ-deficient mouse models (RecQ1, WRN and RecQ4). We find abnormal cognitive behavior in RecQ-deficient mice in the absence of IR. Interestingly, RecQ dysfunction impairs social ability and induces depressive-like behavior in mice after a single exposure to IR, suggesting that RecQ
proteins play roles in mood and cognition behavior. Further, transcriptomic and metabolomic analyses revealed significant alterations in RecQ-deficient mice, especially after IR exposure. In particular, pathways related to neuronal and microglial functions, DNA damage repair, cell cycle, and reactive
oxygen responses were downregulated in the RecQ4 and WRN mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes,
Aldolase Fructose-Bisphosphate B (Aldob) and
NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our findings suggest that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that
aldolase activity may be associated with these changes, representing a potential therapeutic target.