Abstract

Strains of dogs with hereditary lesion-specific defects in cardiovascular development are used to study the pathogenesis of conotruncal septum defects (including tetralogy of fallot, ventricular septal defect, and persistent truncus arteriosus), pulmonary valve dysplasia, and patent ductus arteriosus. Comparing embryos from affected strains with normal control embryos at comparable stages of development, the investigations progress through classical embryologic studies of the time course of abnormalities in the shape and form of the developing heart, to investigation of the roles of cell proliferation, differential cell death, and formation of intercellular matrix in the genesis of these malformations. Methods used include wax plate reconstruction of the developing heart from serial sections, transmission electron microscopy, scanning electron microscopy of microdissected hearts, and Quantimet analysis of the relative volumes of cell vs extracellular matrix in sections from selected areas of the developing heart. Quantitative morphometric studies of mitotic activity and cell death utilize cytologic techniques. Autoradiography is used to assess cell replication (incorporation of tritiated thymidine into DNA) in sections from selected areas.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL018848-13
Application #
3335685
Study Section
Cardiovascular Study Section (CVA)
Project Start
1977-05-01
Project End
1989-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Werner, Petra; Raducha, Michael G; Prociuk, Ulana et al. (2008) A novel locus for dilated cardiomyopathy maps to canine chromosome 8. Genomics 91:517-21
Werner, Petra; Raducha, Michael G; Prociuk, Ulana et al. (2005) The keeshond defect in cardiac conotruncal development is oligogenic. Hum Genet 116:368-77
Werner, P; Raducha, M G; Shin, D et al. (2004) Assignment of 10 canine genes to the canine linkage and comparative maps. Anim Genet 35:249-51
Buchanan, James W; Patterson, Donald F (2003) Etiology of patent ductus arteriosus in dogs. J Vet Intern Med 17:167-71
Buchanan, J W (2001) Pathogenesis of single right coronary artery and pulmonic stenosis in English Bulldogs. J Vet Intern Med 15:101-4
Otto, C M; Rieser, T M; Brooks, M B et al. (2000) Evidence of hypercoagulability in dogs with parvoviral enteritis. J Am Vet Med Assoc 217:1500-4
Mellersh, C S; Hitte, C; Richman, M et al. (2000) An integrated linkage-radiation hybrid map of the canine genome. Mamm Genome 11:120-30
Werner, P; Mellersh, C S; Raducha, M G et al. (1999) Anchoring of canine linkage groups with chromosome-specific markers. Mamm Genome 10:814-23
Werner, P; Raducha, M G; Prociuk, U et al. (1999) Comparative mapping of the DiGeorge region in the dog and exclusion of linkage to inherited canine conotruncal heart defects. J Hered 90:494-8
Werner, P; Raducha, M G; Prociuk, U et al. (1999) A comparative approach to physical and linkage mapping of genes on canine chromosomes using gene-associated simple sequence repeat polymorphisms illustrated by studies of dog chromosome 9. J Hered 90:39-42

Showing the most recent 10 out of 21 publications