Variation of sexual dimorphism and asymmetry in disease expression of inflammatory arthritis among laboratory mouse models with different genomic backgrounds

Wei Dong; Cheng Tian; Z Galvin Li; David Brand; Yanhong Cao; Xiaoyun Liu; Jiamin Ma; Andy Chai; Linda K Myers; Jian Yan; Karen Hasty; John Stuart; Yan Jiao; Weikuan Gu; Xiaojun Cai

doi:10.1186/s42826-023-00185-0

Variation of sexual dimorphism and asymmetry in disease expression of inflammatory arthritis among laboratory mouse models with different genomic backgrounds

Lab Anim Res. 2023 Dec 20;39(1):35. doi: 10.1186/s42826-023-00185-0.

Authors

Wei Dong^{1

2}, Cheng Tian³, Z Galvin Li¹, David Brand^{4

5}, Yanhong Cao⁶, Xiaoyun Liu^{7

8}, Jiamin Ma¹, Andy Chai¹, Linda K Myers⁵, Jian Yan¹, Karen Hasty¹, John Stuart⁵, Yan Jiao⁹, Weikuan Gu^{10

11}, Xiaojun Cai¹²

Affiliations

¹ Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
² Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, 150001, Heilongjiang, China.
³ St. Jude Children's Research Hospital, Memphis, TN, USA.
⁴ Research Service, Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA.
⁵ Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
⁶ Institute of Kaschin-Beck Disease, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Laboratory of Etiologic Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618104), Harbin Medical University, Harbin, 150081, China.
⁷ Center for Clinical Precision Medication, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
⁸ Clinical Pharmacy (School of Integrative Pharmacy, Institute of Integrative Pharmaceutical Research), Guangdong Pharmaceutical University, Guangzhou, 510006, China.
⁹ Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. Yjiao2@uthsc.edu.
¹⁰ Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. wgu@uthsc.edu.
¹¹ Research Service, Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. wgu@uthsc.edu.
¹² Heilongjiang Academy of Sciences of Traditional Chinese Medicine, No. 72 Xiangan Street, Xiangfang District, Harbin, 150036, China. ssycxj@163.com.

Abstract

Sex difference has shown in the arthritis diseases in human population and animal models. We investigate how the sex and symmetry vary among mouse models with different genomic backgrounds. Disease data of sex and limbs accumulated in the past more than two decades from four unique populations of murine arthritis models were analyzed. They are (1) interleukin-1 receptor antagonist (IL-1ra) deficient mice under Balb/c background (Balb/c KO); (2) Mice with collagen II induced arthritis under DBA/1 background; (3) Mice with collagen II induced arthritis under C57BL/6 (B6) background and (4) A F2 generation population created by Balb/c KO X DBA/1 KO. Our data shows that there is a great variation in sexual dimorphism for arthritis incidence and severity of arthritis in mice harboring specific genetic modifications. For a F2 population, the incidence of arthritis was 57.1% in female mice and 75.6% in male mice. There was a difference in severity related to sex in two populations: B6.DR1/ B6.DR4 (P < 0.001) and F2 (P = 0.023) There was no difference Balb/c parental strain or in collagen-induced arthritis (CIA) in DBA/1 mice. Among these populations, the right hindlimbs are significantly higher than the scores for the left hindlimbs in males (P < 0.05). However, when examining disease expression using the collagen induced arthritis model with DBA/1 mice, sex-dimorphism did not reach statistical significance, while left hindlimbs showed a tendency toward greater disease expression over the right. Sexual dimorphism in disease expression in mouse models is strain and genomic background dependent. It sets an alarm that potential variation in sexual dimorphism among different racial and ethnic groups in human populations may exist. It is important to not only include both sexes and but also pay attention to possible variations caused by disease expression and response to treatment in all the studies of arthritis in animal models and human populations.

Keywords: Inflammation; Mouse model; Rheumatoid arthritis; Severity; Sex difference.

Abstract

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