ARS | Publication request: Screening and Characterization of Spontaneous Porcine Congenital Heart Defects for Gene Identification and Models of Human Disease

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: February 1, 2010
Publication Date: March 20, 2010
Citation: Metlay, L.A., Goldman, B.I., Cassady, J., Miles, J.R., Rohrer, G.A., Vallet, J.L., Ackerman, K.G. 2010. Screening and Characterization of Spontaneous Porcine Congenital Heart Defects for Gene Identification and Models of Human Disease [abstract]. Society for Pediatric Pathology Spring Meeting, Washington, D.C., 3/20-21/2010. #27. (available: http://www.spponline.org/2010-1SpringMtg/FullAbstractsAcceptedPresentationOrder.pdf)

Technical Abstract: Background: Rodent models of human congenital birth defects have been instrumental for gene discovery and investigation of mechanisms of disease. However, these models are limited by their small size making practiced intervention or detailed anatomic evaluation difficult. Swine have similar anatomy and physiology to humans, and their size at birth is comparable to a human neonate. Design: In a pilot screen, we developed methodology to conduct a now ongoing large scale screen for specific structural birth defects in piglets that are either stillborn or die in the first 48 hours of life or are euthanized for other research purposes. Piglets are from research herds that are non-genetically modified, relatively inbred, and have known pedigree information. Piglets are screened on site for the presence of cleft palate, myelomeningocele, megabladder/hydroureter/hydronephrosis, and congenital diaphragmatic hernia. Hearts are excised and sent to the University of Rochester for detailed examination by pathologists. Results: Materials from over 950 piglets have been examined and structural birth defects have been identified including cleft palate and megabladder with hydroureter and hydronephrosis. Of significant interest, examination of 623 hearts from one herd revealed 8 congenital heart defects. Of these, 6 had perimembranous ventricular septal defects (VSD), one had an atrioventricular canal defect, and one had a bicuspid pulmonary valve. Two of these piglets were born alive. The six piglets with perimembranous VSD were highly related and shared common ancestors making an autosomal recessive inheritance likely. Two of these had identical defects with marked trabecular extension, and these were farrowed by sister sows and sired by boars derived from a common ancestor. Conclusion: We have implemented a large scale screen for spontaneous genetic congenital heart defects in swine. To date, we have identified 15 congenital heart defects including one family with potentially heritable perimembranous VSD. Recently available porcine genetic tools will allow for susceptibility locus mapping and candidate gene identification. The detailed anatomic pathological review of inbred animals with newly published genomes is a novel approach to developing genetic models of human disease.