Establishment and identification of an animal model of Hirschsprung disease in suckling mice.

Establishment and identification of an animal model of Hirschsprung disease in suckling mice.
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DOI:
10.1038/s41390-023-02728-6
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发表时间:
2023-12
期刊:
影响因子:
3.6
通讯作者:
Zhang, Yan
Zhang, Yan
中科院分区:
医学3区
文献类型:
--
作者:
Lan, Chaoting;Wu, Yuxin;Liu, Yanqing;Wang, Ning;Su, Meiling;Qin, Dingjiang;Zhong, Weiyong;Zhao, Xinying;Zhu, Yun;He, Qiuming;Xia, Huimin;Zhang, Yan

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先天性巨结肠是一种先天性肠道畸形。以往的HSCR动物模型需要对成年动物进行有创性操作。本研究的目的是建立一种符合HSCR患者临床表现的早发性动物模型。将新生小鼠随机分为苯扎氯铵(BAC)组和对照组。采用体重变化、胭脂红排泄时间、CT扫描、苏木精-伊红染色、免疫荧光染色等方法评价模型的作用。利用大卫6.8数据库分析HSCR小鼠的差异表达基因(DEG),并与HSCR患者的DEG进行比较。BAC组小鼠体重较低,胭脂红排泄时间较长。BAC组出现远端结肠狭窄和近端结肠扩大。BAC治疗4周后远端结肠神经元明显减少,12周后几乎完全消失。小鼠模型和HSCR患者的转录组谱在改变的基因表达方面是相似的。成功地建立了一种经济、可靠的HSCR动物模型,该模型具有与HSCR患者相似的临床特征。首次在BALB/c小鼠中建立了先天性巨结肠动物模型。该模型是一种操作简便、符合临床表现的早发性HSCR动物模型。小鼠模型和HSCR患者的转录组谱在改变的基因表达方面是相似的。
Hirschsprung disease (HSCR) is a congenital intestinal malformation. Previous HSCR animal model needs invasive operation on adult animal. The aim of this study is to establish an early-onset animal model which is consistent with the clinical manifestation of HSCR patients. The neonatal mice were randomly divided into the benzalkonium chloride (BAC) group, treated with BAC via enema, and the control group, treated with saline. Weight changes, excretion time of carmine, CT scan, hematoxylin-eosin staining and immunofluorescence staining were used to evaluate the effect of the model. Differentially expressed genes (DEGs) in the HSCR mice were analyzed by using DAVID 6.8 database and compared with DEGs from HSCR patients. The weight of mice was lower and the excretion time of carmine was longer in the BAC group. Moreover, distal colon stenosis and proximal colon enlargement appeared in the BAC group. Neurons in the distal colon decreased significantly after 4 weeks of BAC treatment and almost disappeared completely after 12 weeks. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression. An economical and reliable HSCR animal model which has similar clinical characteristics to HSCR patients was successfully established. The animal model of Hirschsprung disease was first established in BALB/c mice. This model is an animal model of early-onset HSCR that is easy to operate and consistent with clinical manifestations. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression.
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