4:00pm - 5:00pm|
The Aab CVRI Seminar Series
SPEAKER: Kirk M. McHugh, Ph.D.
Professor & Director
Division of Anatomy
Department of Biomedical Education & Anatomy
The Ohio State University
Professor & Directors
Nephrology & Urology Research Affinity
Center for Biomedical and Translational Research
Nationwide Children's Hospital
TITLE OF TALK: "Megabladder Mouse Model of Abnormal Detrusor and Cardiac Outflow Tract Smooth Muscle Development"
Research Summary: My research efforts focus on the normal development and pathogenesis of the urogenital system. Urinary tract malformations, obstructive nephropathy, and renal hypoplasia/dysplasia comprise over 50% of the children with end-stage renal disease worldwide. These defects are extremely important in the terms of health care costs, with end-stage renal disease costing 1.5 billion dollars annually. Studies in my lab focus on congenital defects in bladder development and the resulting sequelae associated with obstructive nephropathy and chronic kidney disease (CKD). We have identified a highly unique mouse model known as the megabladder (mgb) that represents the first animal model of congenital obstructive nephropathy. We use a wide range of genetic and molecular approaches to study the pathogenic changes in mgb-/- renal function that are associated with the development of chronic kidney disease (CKD) and end stage renal disease (ESRD). These studies have lead to a novel renal adaptation model that involves the integrated balance between TGF-mediated pathogenesis, retinoic acid mediated remodeling/repair and steroid hormone modulation. Genetic studies of the mgb-/- mouse mutation indicate that these animals possess a complex deletion/translocation defect associated with chromosomes 16 and 11. The deletion/translocation site on chromosome 11 occurs 1+ Mb upstream of the myocardin gene and appears to have disrupted a long-range, tissue-specific enhancer element that is responsible for up-regulation of myocardin expression in the bladder. These genetic defects result in the production of a hypomorphic allele that reduces myocardin expression in the bladder by 75%. Further reduction in myocardin expression to 90% results in the appearance of a second defect, patent ductus arteriosus, that results in early postnatal lethality in these animals.
|Location: ||CVRI Conf. Room # G.11211/G.11213 MRBX/Delmonte Bldg - (Ground floor)|
Posted by: Jacqueline Velazquez, Cardiovascular Research Institute, 9-Jan-17 1:52pm ET