Characterization of Esophageal Defects in the Crouzon Mouse Model
Characterization of Esophageal Defects in the Crouzon Mouse Model
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DOI：
10.1002/bdra.23172
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发表时间：
2013-09-01
影响因子：
--
通讯作者：
Gong, Siew-Ging
中科院分区：
文献类型：
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作者：
Dab, Sandeep;Sokhi, Ramanpreet;Gong, Siew-Ging
成纤维细胞生长因子受体（FGFR）的突变与人类颅缝早闭性出生缺陷如Crouzon综合征有关。一些轶事和病例报告表明，FGFR相关的颅缝早闭性出生缺陷中胃肠道疾病的发生率较高。本研究的目的是探讨人Crouzon综合征小鼠模型中FGFR2基因290位密码子突变引起的食管缺损的特征。方法采用组织学染色、细胞增殖标记物免疫组化、通过应变仪测量电诱发的收缩力，在功能上也是如此。与野生型同窝出生的小鼠相比，Hesophagus的食管明显较小，但管腔较宽。与野生型食管相比，HET食管显示增殖减少和Sonic Hedgehog表达增加。组织学研究显示肌肉层中胶原蛋白的数量减少和解体。功能分析显示，HET的收缩特性改变，诱发收缩力反应的峰值幅度降低，持续时间延长，刺激threshold.CONCLUSION突变体的食管中观察到的缺陷可以解释一些在人类中观察到的临床症状，例如，反复呕吐，胃食管反流，食管狭窄。总之，我们的研究结果为成纤维细胞生长因子信号传导在食管生长和形成模式中的重要性提供了证据，为颅缝早闭患者的胃肠道临床发现提供了可能的科学依据。此外，研究结果还为颅缝早闭缺陷患者胃肠道问题的临床管理的任何变化提供了合理的科学依据。(c)2013 Wiley Periodicals，Inc.
BACKGROUNDMutations in Fibroblastic Growth Factor Receptors (FGFR) have been associated with human craniosynostotic birth defects like Crouzon syndrome. Several anecdotes and case reports have indicated higher incidence of gastrointestinal tract disorders in FGFR-associated craniosynostotic birth defects. Our objective was to characterize esophageal defects in a mouse model of human Crouzon syndrome, with a mutation in codon 290 of FGFR2.METHODSDissected esophagi of Fgfr2(W290R) postnatal heterozygous (HET) and wild-type mice were analyzed by histological staining, immunohistochemically with cell proliferation marker, and functionally by strain gauge measures of electrically evoked contractile force.RESULTSThe esophagi of HETs were noticeably smaller but with wider lumen than those of wild-type littermates. The HET esophagi showed a decrease in proliferation and an increase in expression of Sonic Hedgehog as compared to wild-type esophagi. Histological investigations revealed reduced amounts and disorganization of collagen in muscle layers. Functional analysis revealed altered contractile properties in HET with reduced peak amplitude and prolonged duration of evoked contractile force response and lower stimulation threshold.CONCLUSIONThe defects observed in the esophagus of the mutant may explain some of the clinical symptoms observed in humans, for example, recurrent vomiting, gastroesophageal reflux, and esophageal strictures. Taken together, our results provide evidence for the importance of Fibroblastic Growth Factor signaling in the growth and patterning of the esophagus, providing a possible scientific basis for the gastrointestinal tract clinical findings in craniosynostotic patients. Furthermore, the findings also provide a sound scientific rationale for any changes in the clinical management of gastrointestinal tract problems in patients with craniosynostotic defects. (c) 2013 Wiley Periodicals, Inc.