Journal of Capital Medical University ›› 2026, Vol. 47 ›› Issue (4): 715-721.doi: 10.3969/j.issn.1006-7795.2026.04.012

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Construction of the IL-10rb genes mouse model with allergic asthma disease based on CRISPR/Cas9 technology

Zhang Xu1,2， Li Jingyun1， Tan Juan2， Yu Boyang1， Zhang Yuan2，Zhang Luo1，2,3*   

  1. 1.Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing Institute of Otolaryngology, Beijing 100005, China；2.Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; 3.Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
  • Received:2026-04-08 Revised:2026-05-12 Online:2026-08-21 Published:2026-07-26
  • Supported by:
    This study was supported by the Young Scientists Fund of the National Natural Science Foundation of China (81800886),  Natural Science Foundation of Beijing (7164247).

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Abstract: Objective  To generate IL-10rb gene knockout mice (IL-10rb－/－) using CRISPR/Cas9 gene editing technology and to evaluate the impact of this knockout on the pathological manifestations of an ovalbumin (OVA)-induced allergic asthma mouse model.Methods  A targeting gRNA was designed against exons 1-2 of the IL-10rb gene. The CRISPR/Cas9 system was microinjected into fertilized eggs of C57BL/6J mice.  F0 positive mice with the IL-10rb－/－ genotype were identified and selected by polymerase chain reaction (PCR) at 7 day after birth. The mice were divided into four groups: wild-type (WT) group, IL-10rb－/－ group, WT-OVA asthma group, and IL-10rb－/－-OVA asthma group. Lung function testing as well as hematoxylin-eosin(H&E), periodic acid Schiff(PAS), and Masson staining of lung tissues were performed to assess airway inflammatory infiltration, goblet cell metaplasia, and collagen deposition.Results  PCR identification confirmed the successful generation of a stably heritable IL-10rb homozygous knockout mouse strain. Lung function tests showed that compared with the WT group, the IL-10rb－/－ group, WT-OVA asthma group, and IL-10rb－/－-OVA asthma group all exhibited significantly decreased respiratory system compliance (P<0.05). Compared with the WT-OVA group, the IL-10rb－/－-OVA group showed a further decrease in respiratory system compliance (P<0.05). In terms of main airway resistance, compared with the WT group, airway resistance and tissue elasticity in the WT-OVA group and the IL-10rb－/－-OVA group were significantly increased  (P<0.05). Lung histopathology revealed that compared with the WT group, the inflammatory cell infiltration in  the IL-10rb－/－ group, WT-OVA group, and IL-10rb－/－-OVA group was significantly increased. Airway goblet cell metaplasia was more pronounced in the IL-10rb－/－-OVA group  than that in the WT-OVA group. Collagen deposition was markedly enhanced in the OVA-sensitized groups (WT-OVA and IL-10rb－/－-OVA) compared with the WT and IL-10rb－/－ groups.Conclusion IL-10rb gene knockout mice can be successfully generated using CRISPR/Cas9 gene editing technology. These mice can recapitulate the typical pathological features of allergic asthma and  serve as an animal model for further investigating the pathogenesis of allergic asthma and developing targeted intervention strategies.

Key words: CRISPR/Cas9, IL-10rb, gene knockout, allergic asthma, airway inflammation, animal model

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