title: Renal failure causes early death of bcl-2 deficient mice.
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 organism.
authors.affiliation: Theodor-Boveri-Institut für Biowissenschaften, Biozentrum, Bayerische Julius-Maximilians-Universität, Am Hubland, 97074 Würzburg, Germany. lev.fedorov@med.uni-jena.de
authors.forename: Lev M
authors.initials: LM
authors.lastname: Fedorov
authors.forename: Carolin
authors.initials: C
authors.lastname: Schmittwolf
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Wolf-Hans
authors.initials: WH
authors.lastname: Thomas
authors.forename: Albrecht M
authors.initials: AM
authors.lastname: Müller
authors.forename: Harald
authors.initials: H
authors.lastname: Schubert
authors.forename: Jos
authors.initials: J
authors.lastname: Domen
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
mesh_terms: 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
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2