Document Detail


Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal atresia in the fibroblast growth factor receptor 2IIIb-/- mouse model.
MedLine Citation:
PMID:  23021139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal atresia formation. To test this, we rendered Fgfr2IIIb(-/-) embryos haploinsufficient for the Raldh2 and examined these embryos for the incidence and severity of duodenal atresia.
METHODS: Control embryos, Fgfr2IIIb(-/-) mutants, and Fgfr2IIIb(-/-); Raldh2(+/-) mutants were harvested at embryonic day 18.5, genotyped, and fixed overnight. Intestinal tracts were isolated. The type and severity of duodenal atresia was documented.
RESULTS: A total of 97 Fgfr2IIIb(-/-) embryos were studied; 44 had duodenal atresias, and 41 of these presented as type III. In the 70 Fgfr2IIIb(-/-); Raldh2(+/-) embryos studied, a lesser incidence of duodenal atresia was seen (15 of 70; P = .0017; Fisher exact test). Atresia severity was also decreased; there were 12 embryos with type I atresias, 3 with type II atresias, and 0 with type III atresias (P < 2.81E-013; Fisher exact test).
CONCLUSION: Haploinsufficiency of Raldh2 decreases the incidence and severity of duodenal atresia in the Fgfr2IIIb(-/-) model. The ability to alter defect severity through manipulation of a single gene in a specific genetic background has potentially important implications for understanding the mechanisms by which intestinal atresias arise.
Authors:
Amy L Reeder; Robert A Botham; Krzysztof M Zaremba; Peter F Nichol
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Surgery     Volume:  152     ISSN:  1532-7361     ISO Abbreviation:  Surgery     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2012-12-13     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  768-75; discussion 775-6     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 Mosby, Inc. All rights reserved.
Affiliation:
Department of Surgery, Section of Pediatric Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Oxidoreductases / deficiency*,  genetics*
Animals
Duodenal Obstruction / congenital*,  embryology,  genetics*,  metabolism
Female
Haploinsufficiency
Imaging, Three-Dimensional
In Situ Hybridization
Intestinal Atresia / embryology,  genetics*,  metabolism
Male
Mice
Mice, Knockout
Penetrance
Pregnancy
Receptor, Fibroblast Growth Factor, Type 2 / deficiency*,  genetics*
Grant Support
ID/Acronym/Agency:
1K08DK087854-03/DK/NIDDK NIH HHS; K08 DK087854/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.1.36/RALDH2 protein, mouse; EC 2.7.1.-/keratinocyte growth factor receptor; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 2
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