RecQ dysfunction contributes to social and depressive-like behavior and affects aldolase activity in mice

Yujun Hou, Jae Hyeon Park, Xiuli Dan, Xixia Chu, Beimeng Yang, Mansoor Hussain, Deborah L. Croteau, Vilhelm A. Bohr

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number106092
JournalNeurobiology of Disease
StatePublished - May 2023
Externally publishedYes

Bibliographical note

Funding Information:
We thank Alfred May and Tomasz Kulikowicz for performing irradiations. We thank Dr. Kulikowicz - for reading the paper. This research was supported by the Intramural Research Program of the National Institute on Aging , NIH (V.A.B.). Y.H. was supported by the National Natural Science Foundation of China (# 82171405 ), the Lingang Laboratory (# LG-QS-202205-10 ), and the Fundamental Research Funds for the Central Universities .

Publisher Copyright:
© 2023 The Authors


  • Aldolase activity
  • DNA damage
  • Depressive-like behavior
  • RecQ helicases
  • WRN

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural


Dive into the research topics of 'RecQ dysfunction contributes to social and depressive-like behavior and affects aldolase activity in mice'. Together they form a unique fingerprint.

Cite this