Renal failure causes early death of bcl-2 deficient mice

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 2006
Externally publishedYes

Fingerprint

Renal Insufficiency
Cause of Death
Polycystic Kidney Diseases
Tissue
Kidney
Repressor Proteins
Cell death
Lymphoid Tissue
Growth
Animals
Transgenes
Knockout Mice
Genes
Aging of materials
Transgenic Mice
Apoptosis
Radiation
Cell Death
Mortality

Keywords

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

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

Cite this

Fedorov, L., Schmittwolf, C., Amann, K., Thomas, W. H., Müller, A. M., Schubert, H., ... 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

Renal failure causes early death of bcl-2 deficient mice. / Fedorov, Lev; Schmittwolf, Carolin; Amann, Kerstin; Thomas, Wolf Hans; Müller, Albrecht M.; Schubert, Harald; Domen, Jos; Kneitz, Burkhard.

In: Mechanisms of Ageing and Development, Vol. 127, No. 7, 07.2006, p. 600-609.

Research output: Contribution to journalArticle

Fedorov, L, Schmittwolf, C, Amann, K, Thomas, WH, Müller, AM, Schubert, H, Domen, J & Kneitz, B 2006, 'Renal failure causes early death of bcl-2 deficient mice', Mechanisms of Ageing and Development, vol. 127, no. 7, pp. 600-609. https://doi.org/10.1016/j.mad.2006.02.009
Fedorov L, Schmittwolf C, Amann K, Thomas WH, Müller AM, Schubert H et al. Renal failure causes early death of bcl-2 deficient mice. Mechanisms of Ageing and Development. 2006 Jul;127(7):600-609. https://doi.org/10.1016/j.mad.2006.02.009
Fedorov, Lev ; Schmittwolf, Carolin ; Amann, Kerstin ; Thomas, Wolf Hans ; Müller, Albrecht M. ; Schubert, Harald ; Domen, Jos ; Kneitz, Burkhard. / Renal failure causes early death of bcl-2 deficient mice. In: Mechanisms of Ageing and Development. 2006 ; Vol. 127, No. 7. pp. 600-609.
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