Renal failure causes early death of bcl-2 deficient mice.
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 organism.
Fedorov
Lev M
LM
Theodor-Boveri-Institut für Biowissenschaften, Biozentrum, Bayerische Julius-Maximilians-Universität, Am Hubland, 97074 Würzburg, Germany. lev.fedorov@med.uni-jena.de
Schmittwolf
Carolin
C
Amann
Kerstin
K
Thomas
Wolf-Hans
WH
Müller
Albrecht M
AM
Schubert
Harald
H
Domen
Jos
J
Kneitz
Burkhard
B
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D003433:Crosses, Genetic; D006130:Growth Disorders / Q000235:genetics / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008136:Longevity / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency*; D051437:Renal Insufficiency / Q000235:genetics* / Q000473:pathology
D019253:Proto-Oncogene Proteins c-bcl-2