Postnatal development and progression of renal dysplasia in cyclooxygenase-2 null mice.


BACKGROUND Genetic ablation of cyclooxygenase-2 (COX-2) resulted in cystic renal dysplasia and early death in adult mice. The ontologic development of the renal pathology and the biochemical and physiological abnormalities associated with the dysplasia are unknown. METHODS Mice homozygous for a targeted deletion of COX-2 (-/-) were compared with wild-type littermates (+/+). Somatic and kidney growth and renal histology were studied at the day of birth and at a number of postnatal ages. Systolic blood pressure, urinalysis, urine osmolality, serum and urine chemistries, and inulin clearance were evaluated in adult animals. RESULTS Beginning at postnatal day 10 (PN10), kidney growth was suppressed in -/- animals, while somatic growth and heart growth were unaffected. By PN10, -/- kidneys had thin nephrogenic cortexes and crowded, small, subcapsular glomeruli. The pathology increased with age with progressive outer cortical dysplasia, cystic subcapsular glomeruli, loss of proximal tubular mass, and tubular atrophy and cyst formation. Adult -/- kidneys had profound diffuse tubular cyst formation, outer cortical glomerular hypoplasia and periglomerular fibrosis, inner cortical nephron hypertrophy, and diffuse interstitial fibrosis. The glomerular filtration rate was reduced by more than 50% in -/- animals (6.82 +/- 0.65 mL/min/kg) compared with wild-type controls (14.7 +/- 1.01 mL/min/kg, P < 0. 001). Plasma blood urea nitrogen and creatinine were elevated in null animals compared with controls. Blood pressure, urinalysis, urine osmolality, and other plasma chemistries were unaffected by the deletion of COX-2. CONCLUSIONS Deficiency of COX-2 results in progressive and specific renal architectural disruption and functional deterioration beginning in the final phases of nephrogenesis. Tissue-specific and time-dependent expression of COX-2 appears necessary for normal postnatal renal development and the maintenance of normal renal architecture and function.

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@article{Norwood2000PostnatalDA, title={Postnatal development and progression of renal dysplasia in cyclooxygenase-2 null mice.}, author={Victoria F. Norwood and Scott G. Morham and Oliver Smithies}, journal={Kidney international}, year={2000}, volume={58 6}, pages={2291-300} }