Hedgehog pathway antagonist-induced oromandibular limb hypogenesis in mouse
10.3760/cma.j.issn.1002-0098.2018.01.008
- VernacularTitle: 外源性Hedgehog抑制剂诱导小鼠口下颌-肢体发育不全模型建立的效果观察
- Author:
Yuanjing JIANG
1
;
Chuanqing MAO
1
;
Yongzhen LAI
1
;
Yunpeng WENG
1
;
Shixian ZHANG
2
;
Weihui CHEN
1
Author Information
1. Department of Oral and Maxillofacial Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China
2. Department of Oral and Maxillofacial Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China(Present address: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Fujian Medical University, Fuzhou 350002, China)
- Publication Type:Journal Article
- Keywords:
Models, animal;
Stomatognathic system abnormalities;
Hedgehog proteins;
Oromandibular limb hypogenesis;
Hedgehog signaling pathway
- From:
Chinese Journal of Stomatology
2018;53(1):36-41
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analysis teratogenic effect of GDC-0449 to fetus and set up the animal model of GDC-0449 induced oromandibular limb hypogenesis in mouse for further research of its pathogenesis.
Methods:Twenty-seven pregnant Institute of Cancer Research (ICR) mice were randomly divided into: control group, embryonic day 8.5 (E8.5) exposed groups, E9.5 exposed groups, E10.5 exposed groups, E11.5 exposed groups, E12.5 exposed groups, E13.5 exposed groups, E14.5 exposed groups and E15.5 exposed groups. Each group had 3 mice. Exposed groups were treated with the Hedgehog pathway antagonist GDC-0449 at a single dose 150 mg/kg by oral gavage from E8.5 to E15.5. At E16.5, embryonic phenotypes were analyzed in detail by stereo microscope and histology. After establish an optimal dysmorphogenic concentration, 6 pregnant ICR mice were randomly divided into control group and the optimal group, embryonic phenotypes were analyzed by whole-mount skeletal staining and micro-computed tomography at E18.5.
Results:The mice were exposed to GDC-0449 on E11.5 and E12.5 had a high incidence of cleft palate. GDC-0449 exposed between E9.5 and E10.5 caused craniofacial and limb dysmorphology, including micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. Most interestingly, these are extremely similar to oromandibular limb hypogenesis syndrome.
Conclusions:The results of this study indicate that GDC-0449 can be used to induce micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. This work established a novel mouse model for oromandibular limb hypogenesis.
