Murine models of renal disease: possibilities and problems in studies using mutant mice.
The elucidation of the pathogenesis of human renal disease at the molecular level has been facilitated by the growing field of gene targeting and the development of mouse strains with single-gene deletions - the 'knock-out' mice. Experimental nephrology, therefore, requires well-characterized and reliable models of human renal disease that can be induced reproducibly in mice. Today surgical procedures for the induction of renal ischemia, chronic renal failure, and ureter obstruction are feasible in mice. Models of mesangioproliferative or crescentic glomerulonephritis, glomerulosclerosis, and tubulointerstitial disease are readily available; however, these depend heavily on the mouse genetic background. Attention to the genetic background and appropriate backcrossing are, therefore, of great importance in the design and interpretation of experimental studies, especially in transgenic mice. Simple murine models displaying the clinical features of other human renal diseases such as IgA nephropathy, membranous glomerulonephritis, and renal vasculitis are still lacking. Mouse strains that spontaneously develop distinct renal pathologies similar to lupus nephritis and focal-segmental glomerulosclerosis can be intercrossed with transgenic mice to study the impact of single-gene deletions on the renal phenotype. The present review provides a survey about currently available spontaneous and inducible murine models of renal disease with special attention to problems and future perspectives for their use in transgenic animals.
Anders
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Medizinische Poliklinik der Ludwig-Maximilians-Universität, München, Deutschland. hjanders@clinbio.med.uni-muenchen.de
Schlöndorff
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D058186:Acute Kidney Injury; D000818:Animals; D003928:Diabetic Nephropathies; D004195:Disease Models, Animal; D005921:Glomerulonephritis; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics; D007676:Kidney Failure, Chronic; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial; D014517:Ureteral Obstruction