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 gamma-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 ...Continue Reading
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