Characterization of esophageal defects in the crouzon mouse model. Issue 9 (2nd September 2013)

• Record Type: Journal Article
• Authors: Dab, Sandeep; Sokhi, Ramanpreet; Lee, Jye‐Chang; Sessle, Barry J.; Aubin, Jane E.; Gong, Siew‐Ging
• Is Part Of: Birth defects research. Volume 97:Issue 9(2013:Sep.)
• Page Start: 578
• Page End: 586
• Publication Date: 2013-09-02
• Subjects: Teratology -- Periodicals; Abnormalities, Human -- Research -- Periodicals; Abnormalities, Human -- Periodicals; 616.043
• DOI: 10.1002/bdra.23172
• Languages: English
• ISSNs: 1542-0752

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bdra23172-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Mutations 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 <italic>FGFR</italic>‐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 <italic>FGFR2</italic>.</p> </sec> <sec id="bdra23172-sec-0002" sec-type="section"> <title>METHODS</title> <p>Dissected esophagi of <italic>Fgfr2<sup>W290R</sup></italic> 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.</p> </sec> <sec id="bdra23172-sec-0003" sec-type="section"> <title>RESULTS</title> <p>The 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 <italic>Sonic Hedgehog</italic> 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.</p> </sec> <sec id="bdra23172-sec-0004" sec-type="section"> <title>CONCLUSION</title> <p>The 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 <italic>Fibroblastic Growth Factor</italic> 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. <italic>Birth Defects Research (Part A) 97:578–586, 2013</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>