Fibroblast growth factor receptor 2 IIIb invalidation - A potential cause of familial duodenal atresia
Fibroblast growth factor receptor 2 IIIb invalidation - A potential cause of familial duodenal atresia
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DOI：
10.1016/j.jpedsurg.2004.02.026
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发表时间：
2004-06-01
影响因子：
2.4
通讯作者：
Burns, RC
中科院分区：
文献类型：
--
作者：
Fairbanks, TJ;Kanard, R;Burns, RC
背景/目的：十二指肠闭锁 (DA) 的发生率为每 6,000 名活产婴儿中就有 1 人发生，是新生儿肠梗阻的一个重要的可手术纠正的原因。已有家族性或先天性 DA 的报道，这意味着至少有一些 DA 病例是遗传性、可遗传性异常的结果。控制十二指肠发育的基因尚不完全清楚。众所周知，成纤维细胞生长因子受体 211lb (Fgfr2b) 在包括其他胃肠道 (GIT) 结构在内的多个器官系统的发育中发挥着关键作用。本研究表明 Fgfr2b 在正常十二指肠发育和 DA 发病机制中的关键作用。方法：从 E18.5 阶段的定时妊娠母亲中收获野生型 (Wt) 和 Fgfr2b(-/-) 胚胎，并分析十二指肠表型。结果：Fgfr2b 失活导致 DA 中。 DA 存在于 Fgf2b(-/-) 突变体中，外显率为 35%。 Fgf2b(-/-)突变体的十二指肠表型范围从正常到粘膜网、1型和III型闭锁。结论：Fgfr2b是十二指肠发育的关键调控基因。 Fgfr2b 失效（Fgfr2b(-/-) 突变体）导致可重复的常染色体隐性十二指肠闭锁表型，具有不完全外显率和可变表型。 (C) 2004 Elsevier Inc. 保留所有权利。
Background/Purpose: Duodenal atresia (DA) occurs in 1 in every 6,000 live births and represents a significant surgically correctable cause of intestinal obstruction in the neonate. Familial or congenital DA has been reported, implying that at least some cases of DA are the result of genetic, heritable abnormalities. The genes controlling duodenal development are incompletely understood. Fibroblast growth factor receptor 211lb (Fgfr2b) is known to play a critical role in the development of multiple organ systems including other gastrointestinal tract (GIT) structures. This study shows the key role of Fgfr2b in normal duodenal development and the pathogenesis of DA.Methods: Wild type (Wt) and Fgfr2b(-/-) embryos were harvested from timed pregnant mothers at stage E18.5 and were analyzed for duodenal phenotype.Results: Inactivation of Fgfr2b results in DA. DA is present in the Fgf2b(-/-) mutants with a 35% penetrance. The duodenal phenotype of the Fgf2b(-/-) mutants ranges from normal to a mucosal web, type 1, and type III atresia.Conclusions: Fgfr2b is a critical regulatory gene in the development of the duodenum. Fgfr2b invalidation (Fgfr2b(-/-) mutant) results in a reproducible, autosomal recessive duodenal atresia phenotype with incomplete penetrance and a variable phenotype. (C) 2004 Elsevier Inc. All rights reserved.