第一鳃弓间充质中敲除Fam20b通过抑制糖胺聚糖链的合成导致Pierre Robin序列征

doi:10.13591/j.cnki.kqyx.2026.03.002

摘要/Abstract

摘要：

目的揭示序列相似性家族20成员b(family with sequence similarity member 20-b,Fam20b)基因在第一鳃弓间充质来源的颅颌面器官发育中的作用。方法构建Pax2-Cre;Fam20b^f/f小鼠,利用整体阿尔辛蓝-茜素红染色观察小鼠出生后的骨骼形态学变化,Masson染色观察组织学特征,Ki67/TUNEL检测第一鳃弓内细胞的增殖和凋亡情况,Von-Kossa染色观察额骨矿化程度,阿尔辛蓝染色检测糖胺聚糖链(glycosaminoglycan chains,GAGs)分布范围。结果胚胎第10.5天时,Pax2-Cre;Fam20b^f/f小鼠下颌弓近端间充质细胞发生大量凋亡,导致该小鼠出生后表现Pierre Robin序列征(小颌畸形、舌后坠及腭裂)样表型,并伴有小颅畸形、前囟闭合不全及髁突发育不良等多种颅颌面器官畸形。组织学研究显示该小鼠额骨垂直向生长不足及矿化不良,髁突细胞外基质中GAGs的沉积减少,髁突软骨过早分化及软骨膜下成骨增加。结论在第一鳃弓间充质中敲除Fam20b导致下颌弓近端间充质细胞过度凋亡,从而造成小颌畸形。此外,抑制GAGs合成可以抑制颌面部膜内成骨,但促进软骨膜下成骨。

关键词: Fam20b, 第一鳃弓间充质细胞, 颅颌面器官畸形, Pierre Robin序列征, 细胞凋亡

Abstract:

Objective To reveal the role of family with sequence similarity member 20-b (Fam20b) in the development of craniofacial organs originating from the first branchial arch mesenchyme. Methods Pax2-Cre;Fam20b^f/f mice were generated and analyzed for postnatal skeletal morphology by whole-mount Alcian blue-Alizarin red staining, for histological features by Masson’s trichrome staining, for cell proliferation/apoptosis in the first branchial arch using Ki67/TUNEL assays, and for frontal bone mineralization by Von-Kossa staining, for glycosaminoglycan chains (GAGs) distribution by Alcian blue staining. Results At embryonic day 10.5 (E10.5), extensive apoptosis in proximal mandibular mesenchyme of Pax2-Cre;Fam20b^f/f mice led to a Pierre Robin sequence-like phenotype (micrognathia, glossoptosis and cleft palate) with microcephaly, delayed anterior fontanelle closure and condylar hypoplasia. Furthermore, Pax2-Cre;Fam20b^f/f mice exhibited the impaired vertical growth and hypomineralization of the frontal bone, as well as the reduced GAGs deposition, premature chondrocyte differentiation and enhanced subperichondral ossification in condyle. Conclusion Conditional knockout of Fam20b in the first branchial mesenchyme induced excessive apoptosis in proximal mandibular mesenchyme which resulted in micrognathia. Additionally, impaired ossification and mineralization of the frontal bone, combined with reduced GAGs deposition and premature maturation in condylar cartilage, suggests the suppressed intramembranous ossification and the enhanced subperichondral ossification by the deficient GAG chain synthesis.

Key words: Fam20b, first branchial arch mesenchymal cells, craniofacial malformations, Pierre Robin sequence, apoptosis

中图分类号:

R394

来小芳, 张力文, 沈晓丹, 陈晓艳, 刘超, 肖晶, 刘波. 第一鳃弓间充质中敲除Fam20b通过抑制糖胺聚糖链的合成导致Pierre Robin序列征[J]. 口腔医学, 2026, 46(3): 167-173.

LAI Xiaofang, ZHANG Liwen, SHEN Xiaodan, CHEN Xiaoyan, LIU Chao, XIAO Jing, LIU Bo. Fam20b deficiency in the first branchial arch mesenchyme causes Pierre Robin sequence by suppressing GAGs synthesis[J]. Stomatology, 2026, 46(3): 167-173.

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