Although Cox-2 is generally associated with biologic events such as injury, inflammation, and proliferation, the knockout mouse model surprisingly shows abnormal kidney development. Characterization of two knockout Cox-2 strains of mice revealed striking similarities with renal dysplasia in dogs. In one strain the transcription and translation start sites were deleted. This strain gave the most severe kidney phenotype showing 100% penetrance in mice.. The kidneys were severely underdeveloped with an overabundance of immature glomeruli, few functional nephrons and undeveloped mesenchymal tissue. BUN and creatinine were elevated consistent with renal dysfunction. The mice had a predisposition to secondary pyelonenephritis. In addition to the kidney abnormalities there were cardiac defects in 50% of the Cox-2 adult mice. The homozygous null females were largely infertile. The other strain disrupted the coding of sequences in exon 8 by insertion and deleted 104 bp of sequence in this exon that are critical for Cox-2 function. This strain showed a more complex and variable phenotype, and no heart defects were reported. The kidneys were small and pale. In the mildest form the kidneys showed immature structures consisting of immature glomeruli and tubules, and sometimes were accompanied by a thinning cortex and reduced number of glomeruli compared to wild type. In more severe cases, homozygotes showed tubular atrophy, interstitial inflammation and fibrosis as well as papillary mineralization. Further characterization of these two mouse knockout strains, showed that Cox-2 was critical for postnatal kidney development and function. This would suggest a similar role for Cox-2 in the dog model, as in the newborn dog AMN107 differentiation of the glomeruli is complete by 2 weeks of age, and nephrogenesis is completed by approximately 10 weeks of age. Recently, a mouse strain was genetically engineered to knockdown the expression of Cox-2. This strain was generated by the insertion of a neomycin resistance cassette into the middle of intron 10. The kidney pathology in this strain was compared to a genetically engineered strain that has an active site substitution mutation that shows a severe kidney phenotype as in the Cox-2 null strains. This knockdown strain shows a phenotype that is intermediate between the wild type and Cox-2 strains with severe renal pathology. Cox-2 gene expression is highly developmentally regulated. In the developing rat kidney, Cox-2 mRNA and protein are first detected beginning at mid –gestation, and are found in the subcapsular epithelial structures. A similar pattern of Cox-2 expression has been reported during mouse development. While the role of Cox-2 in organogenesis is not clear, this gene shows high expression during late gestation in the skin, heart, cartilage and the kidney in the rat. The present study presents novel allelic variants in the Cox-2 promoter consisting of insertions or deletions of putative SP1 transcription factor binding sites.