全反式维甲酸诱导综合征型唇腭裂小鼠模型的建立和分析

doi:10.13701/j.cnki.kqyxyj.2024.08.009

口腔医学研究 ›› 2024, Vol. 40 ›› Issue (8): 710-714.DOI: 10.13701/j.cnki.kqyxyj.2024.08.009

全反式维甲酸诱导综合征型唇腭裂小鼠模型的建立和分析

王宇萌^1,2,3, 迟丹丹^1,2,3, 张贝贝^1,2,3, 段小红^2*, 黄永清^1,3*

1.宁夏医科大学口腔医学院宁夏银川 750004;
2.口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学第三附属医院口腔生物学教研室陕西西安 710032;
3.宁夏医科大学总医院口腔医院口腔颌面外科,宁夏口腔疾病研究重点实验室宁夏银川 750004

收稿日期:2024-02-18 出版日期:2024-08-28 发布日期:2024-08-22
通讯作者: *段小红,E-mail: xhduan@fmmu.edu.cn;黄永清,E-mail: yongqinghuang_6510@126.com
作者简介:王宇萌(1995~ ),女,河北人,硕士在读,医师,研究方向:唇腭裂。
基金资助:
国家自然科学基金(编号:81960197、81974145、81771052);陕西省重点研发计划重点产业创新链(群)重点项目(编号: 2021ZDLSF02-13);国家口腔疾病临床研究中心重点项目(编号:LCC202201);宁夏医科大学总医院(自治区临床研究中心)开放课题(编号:2019209)

Establishment and Analysis of A Mouse Model of Syndromic Cleft Lip and Palate Induced by All-trans Retinoic Acid

WANG Yumeng^1,2,3, CHI Dandan^1,2,3, ZHANG Beibei^1,2,3, DUAN Xiaohong^2*, HUANG Yongqing^1,3*

1. Ningxia Medical University, Yinchuan 750004, China;
2. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology & Clinic of Oral Rare Diseases and Genetic Diseases, School of Stomatology, the Fourth Military Medical University, Xi’an 710032, China;
3. Ningxia Key Laboratory of Oral Disease Research; Ningxia Key Laboratory of Craniomaxillofacial Deformities Research; Department of Oral and Maxillafacial Surgery, Hospital of Stomatology, the General Hospital of Ningxia Medical University, Yinchuan 750004, China

Received:2024-02-18 Online:2024-08-28 Published:2024-08-22

摘要/Abstract

摘要： 目的: 建立综合征型唇腭裂小鼠模型并分析其表型特征。方法: 采用灌胃法于孕鼠妊娠10.5 d(gestational days 10.5, GD10.5),以90 mg/kg的全反式维甲酸(all-trans retinoic acid, atRA)或等量玉米油+二甲基亚砜(dimethyl sulfoxide, DMSO)溶剂处理,GD14.5/GD17.5取胎鼠,行体视显微镜、石蜡包埋、切片、苏木精-伊红(hematoxylin-eosin, HE)染色观察胎鼠的全身及腭组织结构和发育情况;免疫荧光染色验证维甲酸受体(retinoic acid receptor alpha,RARα)在小鼠腭部及牙的表达情况。结果: 实验组胎鼠出现腭裂、磨牙发育异常、肢体畸形、心肌致密化不全等表型。实验组RARα表达升高。结论: atRA诱导建立的小鼠腭裂模型具有综合征型唇腭裂的特征,可通过激活RARα受体影响小鼠发育。

关键词: 全反式维甲酸, 综合征型唇腭裂, 先天性心脏病, 磨牙, 成釉细胞

Abstract: Objective: To establish and analyze a mouse model of syndromic cleft lip and palate in mice. Methods: Pregnant mice on gestation day 10.5 (GD10.5) were gavaged with 90 mg/kg of atRA or corn oil and DMSO solvent. Upon euthanasia of pregnant mice on GD17.5, embryos were collected. Stereomicroscope, paraffin embedding and sectioning, and hematoxylin-eosin (HE) staining were used to observe the development of embryos. Immunofluorescence staining was used to verify the expression of retinoic acid receptor alpha (RARα). Results: The embryos in the atRA group showed cleft palate, limb deformities, abnormal molar development, and non-compaction of ventricular myocardium. Immunofluorescence staining showed the expression of RARα increased in molar and palate of embryos of the atRA group. Conclusion: The mouse cleft palate model induced by atRA presents as syndromic cleft lip and palate, and atRA affects the development of mice by activating of RARα receptor.

Key words: all-trans retinoic acid, syndromic cleft lip and palate, congenital heart defects, molar, ameloblasts

王宇萌, 迟丹丹, 张贝贝, 段小红, 黄永清. 全反式维甲酸诱导综合征型唇腭裂小鼠模型的建立和分析[J]. 口腔医学研究, 2024, 40(8): 710-714.

WANG Yumeng, CHI Dandan, ZHANG Beibei, DUAN Xiaohong, HUANG Yongqing. Establishment and Analysis of A Mouse Model of Syndromic Cleft Lip and Palate Induced by All-trans Retinoic Acid[J]. Journal of Oral Science Research, 2024, 40(8): 710-714.

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全反式维甲酸诱导综合征型唇腭裂小鼠模型的建立和分析

Establishment and Analysis of A Mouse Model of Syndromic Cleft Lip and Palate Induced by All-trans Retinoic Acid

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