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Analysis of Cardiorenal Physiological Dysfunction in a Mouse Model of Neonatal‐lethal Congenital Obstructive Nephropathy
Author(s) -
Lui Vanessa,
Lee Amanda,
Polgar Noemi,
Tamashiro KadeeKalia,
Napoli Josephine Andrea,
Walton Chad,
Fogelgren Ben
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.665.13
Subject(s) - cardiorenal syndrome , medicine , urinary system , nephropathy , lung , fetus , kidney , endocrinology , ureter , kidney disease , pathology , biology , urology , pregnancy , genetics , diabetes mellitus
Congenital obstructive nephropathy is the most common cause of pediatric chronic kidney disease and end stage renal disease. This disease is caused by obstruction of the urinary tract during fetal development and most commonly occurs at the ureteropelvic junction (UPJ), where the renal pelvis transitions into the ureter. The exocyst is a highly‐conserved 8‐protein trafficking complex and we recently generated a novel conditional knockout mouse for the central exocyst subunit, Sec10 (Sec10‐CKO). Upon Sec10 deletion in the developing kidney and ureter epithelial cells, the mice displayed late‐gestational congenital UPJ obstructions that caused death 10‐14 hours after birth. To further investigate the physiological consequences of these lethal urinary obstructions, cardiorenal and pulmonary parameters were compared in wild‐type and mutant newborn littermates. Upon necropsies, atrial distension with severe hemorrhaging was grossly visible in the mutants compared to littermate controls, which was also confirmed with histological analysis. We performed M‐mode and Doppler echocardiography on the hearts of newborn mice, which indicated signs of diastolic dysfunction. Assessment of newborn lung mass and surface area showed no significance between control and mutant mice. Although our analysis is ongoing, these preliminary results suggest this new mouse model may be a useful tool in studying the cardiovascular consequences of severe urinary obstructions in humans.