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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/F1125    most recent 00219.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Yang, T. Articles by Briggs, J. P. Search for Related Content PubMed PubMed Citation Articles by Yang, T. Articles by Briggs, J. P.

Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice

¹National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and ²Division of Nephrology, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah

Submitted 14 June 2004 ; accepted in final form 3 November 2004

The present study was undertaken to determine whether the severity of renal failure or hypertension in homozygous cyclooxygenase (COX)-2-deficient (COX-2–/–) mice affected by genetic background or gender. COX-2 deletion was introduced into three congenic genetic backgrounds, 129/Sv (129/COX-2–/–), C57/BL6 (C57/COX-2–/–), and BALB/c (BALB/COX-2–/–), by backcrossing the original mixed-background knockout mice with the respective inbred strains for 9 or 10 generations. Evaluation of the severity of hypertension and renal failure was performed in knockout and wild-type mice at the age of 2.5–3.5 mo. Blood pressure measured by tail-cuff plethysmography was significantly elevated in the male 129/COX-2–/– mice (165.8 ± 9.2 vs. 116 ± 5.1 mmHg, P < 0.05), and to a much lesser extent in the female 129/COX-2–/– mice (127.4 ± 3.3 vs. 102.4 ± 3.3), whereas it was unchanged in the C57- or BALB/COX-2–/– mice regardless of gender. Urinary excretion of albumin, determined by EIA, was remarkably increased in the 129/COX-2–/– (16.4 ± 4.1 vs. 0.16 ± 0.043 mg albumin/mg creatinine, P < 0.001), and to a lesser extent in the male C57/COX-2–/– mice (0.595 ± 0.416 vs. 0.068 ± 0.019). Albumin excretion was not elevated in the male BALB/COX-2–/– or in female COX-2–/– mice on any of the three genetic backgrounds. Histological analysis showed abundant protein casts, dilated tubules, and infiltration of inflammatory cells in the male 129/COX-2–/– mice, but not in COX-2–/– mice in other strains or gender. However, the presence of small glomeruli in the nephrogenic zone was observed in all strains of COX-2 knockout mice, regardless of genetic background and gender. Therefore, we conclude that the severity of hypertension and renal failure in COX-2-deficient mice is influenced by genetic background and gender, whereas the incomplete maturation of outer cortical nephrons appears to be independent of genetic background effects.

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