Renal failure causes early death of bcl-2 deficient mice

Lev M. Fedorov, Carolin Schmittwolf, Kerstin Amann, Wolf Hans Thomas, Albrecht M. Müller, Harald Schubert, Jos Domen, Burkhard Kneitz

    Research output: Contribution to journalArticle

    10 Scopus citations

    Abstract

    BCL-2 functions as a death repressor molecule in an evolutionary conserved cell death pathway. Inactivation of bcl-2 in mice results in pleiotropic effects including postnatal growth retardation, massive apoptosis in lymphoid tissues, polycystic kidney disease (PKD) and shortened lifespan. To evaluate the influence of the affected bcl-2 deficient kidneys on the postnatal development and lifespan of bcl-2 knockout mice we used "the rescue of (n - 1) affected tissues" strategy. According to this strategy bcl-2 heterozygous animals were crossed with H2K-hbcl-2 transgenic mice expressing human BCL-2 in most tissues and organs excluding the kidney. Overexpression of hBCL-2 in bcl-2-/- mice rescues growth retardation, normalizes and protects the hematolymphoid system from γ-radiation. However, the hbcl-2 transgene is not expressed in kidneys and the rescued mice have PKD and a shortened lifespan. Thus, our results indicated that PKD is the main reason of early mortality in bcl-2 deficient mice. Moreover, we have created mouse model, similar to the kidney specific knockout of bcl-2. Such models can be useful to study the influence of bcl-2 or other gene deficiency in individual organs (or tissues) on development and ageing of whole organism.

    Original languageEnglish (US)
    Pages (from-to)600-609
    Number of pages10
    JournalMechanisms of Ageing and Development
    Volume127
    Issue number7
    DOIs
    StatePublished - Jul 1 2006

    Keywords

    • BCL-2
    • Hematolymphoid system
    • Lifespan
    • Polycystic kidney

    ASJC Scopus subject areas

    • Aging
    • Developmental Biology

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  • Cite this

    Fedorov, L. M., Schmittwolf, C., Amann, K., Thomas, W. H., Müller, A. M., Schubert, H., Domen, J., & Kneitz, B. (2006). Renal failure causes early death of bcl-2 deficient mice. Mechanisms of Ageing and Development, 127(7), 600-609. https://doi.org/10.1016/j.mad.2006.02.009