The wt1-heterozygous mouse: a model to study the development of glomerular sclerosis

Aswin L Menke, Annemieke IJpenberg, Stewart Fleming, Allyson Ross, Claire N Medine, Charles E Patek, Lee Spraggon, Jeremy Hughes, Alan R Clarke, Nicholas D Hastie

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    Abstract

    In the present study, it is shown that mice heterozygous for wt1 develop glomerular sclerosis and the nature and time course of events leading to the glomerular scarring are determined. Wt1-heterozygous (wt1het) mice and their wild-type littermates were closely monitored from birth and plasma levels of urea, creatinine, and albumin were compared with histological data and clinical features. One of the first indications of nephropathy in the wt1het mouse was the development of proteinuria, accompanied by progressive elevation of the plasma levels of urea and creatinine. Subsequently, the mice developed albuminuria, which correlated with thickening of the glomerular basement membrane and fusion of the podocyte foot processes. Glomerulosclerosis was a relatively late event, accompanied by severe albuminuria and loss of WT1, nephrin, CD2AP, and alpha-actinin-4.
    Original languageEnglish
    Pages (from-to)667-74
    Number of pages8
    JournalJournal of Pathology
    Volume200
    Issue number5
    DOIs
    Publication statusPublished - 2003

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    Menke, A. L., IJpenberg, A., Fleming, S., Ross, A., Medine, C. N., Patek, C. E., Spraggon, L., Hughes, J., Clarke, A. R., & Hastie, N. D. (2003). The wt1-heterozygous mouse: a model to study the development of glomerular sclerosis. Journal of Pathology, 200(5), 667-74. https://doi.org/10.1002/path.1390