COX-2 gene dosage-dependent defects in kidney development.

Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4–8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2+/+, COX-2+/−, and COX-2−/− mice as well as in C57Bl6 mice treated postnatally with low (5 mg·kg−1·day−1) and high (10 mg·kg−1·day−1) doses of the selective COX-2 inhibitor SC-236. COX-2+/− mice exhibit impaired kidney development leading to reduced glomerular size but, in contrast to COX-2−/− mice, only marginal cortical thinning. Moreover, in COX-2+/− and COX-2−/− kidneys, juxtamedullary glomeruli, which develop in the very early stages of nephrogenesis, also showed a size reduction. In COX-2+/− kidneys at the age of 8 days, we observed significantly less expression of COX-2 mRNA and protein and less PGE2 and PGI2 synthetic activity c...