Society of University SurgeonsDefective sonic hedgehog signaling in esophageal atresia with tracheoesophageal fistula*,**
Section snippets
Adriamycin induction of EA/TEF
After protocol approval was obtained from our Institutional Animal Care and Use Committee, time-dated pregnant Sprague-Dawley rats (day 0.5 corresponding with noon of the day of discovery of a vaginal plug) were obtained from Charles River Laboratories (Wilmington, Mass). On gestational days 6 through 9, the experimental rats were injected intraperitoneally with 2 mg/kg of Adriamycin. Control animals were not injected. Litters of embryos from both groups were harvested on embryonic day 12.5
Semiquantitative RT-PCR
By semiquantitative fluorescence-activated real-time RT-PCR, there were no differences noted among levels of Shh, patched, smoothened, and Gli-1 or Gli-3 at e12.5 (data not shown). However, our data for Gli-2 revealed a statistically significant lower level of expression in the fistula tract when compared with the esophagus (P =.019; Fig 1).
Discussion
The pathogenesis of congenital EA/TEF remains an enigma. Although there are many theories of its development, no single theory encompasses all of the variations nor the associated variable penetrance of the VACTERL syndrome. Most cases of EA/TEF occur sporadically, so it is highly unlikely that there is a simple, inheritable genetic mechanism, which lends support to the notion that the cause is multifactorial. With the discovery of the teratogen-induced rodent model of EA/TEF, we have been able
Acknowledgements
The monoclonal antibody, 5E1, a sonic hedgehog inhibitor, which was developed by Thomas M. Jessell, was obtained from the Developmental Studies Hybridoma Bank that was developed under the auspices of the National Institute of Child Health and Human Development and maintained by The University of Iowa, Department of Biological Sciences.
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Cited by (0)
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Reprint requests: George K. Gittes, MD, The Children's Mercy Hospital, Laboratory for Surgical Organogenesis, 2401 Gillham Road, Kansas City MO 64108.
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0039-6060/2003/$30.00 + 0