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Updated: Aug 9, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Renal failure causes early death of bcl-2 deficient mice
Lev M Fedorov1, Carolin Schmittwolf, Kerstin Amann
1Theodor-Boveri-Institut für Biowissenschaften, Biozentrum, Bayerische Julius-Maximilians-Universität, Am Hubland, 97074 Würzburg, Germany. lev.fedorov@med.uni-jena.de
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.
Insights
The absence of BCL-2 causes polycystic kidney disease (PKD) and early death in mice. Restoring BCL-2 in other organs did not prevent PKD, confirming its critical role in kidney health and overall lifespan.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- BCL-2 is a key regulator of apoptosis, a programmed cell death process.
- Bcl-2 deficiency in mice leads to growth defects, lymphoid apoptosis, polycystic kidney disease (PKD), and reduced lifespan.
Purpose of the Study:
- To investigate the specific role of kidney BCL-2 in the development and lifespan of BCL-2 deficient mice.
- To determine if BCL-2 deficiency in kidneys is the primary cause of early mortality.
Main Methods:
- Utilized a "rescue of (n-1) affected tissues" strategy by crossing BCL-2 heterozygous mice with H2K-hBCL-2 transgenic mice.
- The transgenic mice expressed human BCL-2 (hBCL-2) in most tissues, but not in the kidneys.
- Evaluated the effects of this genetic manipulation on postnatal development, hematolymphoid system, kidney function, and lifespan.
Main Results:
- Overexpression of hBCL-2 rescued growth retardation and protected the hematolymphoid system from radiation damage.
- However, the absence of hBCL-2 expression in the kidneys of rescued mice resulted in persistent PKD and a shortened lifespan.
- This indicates that kidney-specific BCL-2 deficiency is the critical factor for early mortality.
Conclusions:
- Polycystic kidney disease (PKD) is the primary cause of early mortality in BCL-2 deficient mice.
- The study successfully created a mouse model mimicking kidney-specific BCL-2 deficiency.
- This model is valuable for studying the impact of organ-specific gene deficiencies on organismal development and aging.
