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Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice
C M Sorenson1, S A Rogers, S J Korsmeyer
1Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.
Abstract:
Apoptosis of the developing metanephric kidney plays an important role in renal organogenesis. The bcl-2 is an oncogene that inhibits apoptotic cell death in a variety of settings. The bcl-2 (-/-) mice complete embryonic development but, in contrast to bcl-2 (+/-) and bcl-2 (+/+) littermates, manifest growth retardation, hypopigmentation of hair, lymphoid apoptosis, abnormal kidney morphology, and renal failure postnatally. To provide insight into the mechanism for the latter abnormalities, we examined metanephric kidneys from bcl-2 (-/-), bcl-2 (+/-), and bcl-2 (+/+) mice, as well as embryonic day 12 (E12) mouse embryos, and compared growth and development of metanephroi in vitro. Kidneys from bcl-2 (+/-) mice developed normally. In contrast, development of kidneys from bcl-2 (-/-) mice was abnormal as reflected by a marked reduction of renal size in newborns compared with kidneys of bcl-2 (+/-) littermates. In addition, kidneys from bcl-2 (-/-) mice contained far fewer nephrons and had smaller nephrogenic zones. Although metanephroi obtained from E12 bcl-2 (+/-) and bcl-2 (-/-) mouse embryos were comparable in size, apoptosis of cells within metanephric blastemas of metanephroi from E12 bcl-2 (-/-) embryos was strikingly enhanced compared with that in blastemas of metanephroi from bcl-2 (+/-) embryos. During 3 days in culture, growth and development of metanephroi from bcl-2 (-/-) embryos were visibly reduced compared with those from bcl-2 (+/-) embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The bcl-2 oncogene is crucial for kidney development. Its absence in bcl-2 (-/-) mice leads to increased apoptosis, resulting in abnormal kidney morphology and renal failure.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Apoptosis is vital for renal organogenesis.
- The bcl-2 oncogene regulates apoptotic cell death.
- bcl-2 knockout mice exhibit developmental defects.
Purpose of the Study:
- Investigate the role of bcl-2 in kidney development.
- Elucidate the mechanism behind renal abnormalities in bcl-2 (-/-) mice.
Main Methods:
- Examined metanephric kidneys from bcl-2 (-/-), bcl-2 (+/-), and bcl-2 (+/+) mice.
- Compared metanephroi growth and development in vitro.
- Assessed apoptosis levels in metanephric blastemas.
Main Results:
- bcl-2 (-/-) mice showed reduced kidney size and fewer nephrons.
- Nephrogenic zones were smaller in bcl-2 (-/-) kidneys.
- Enhanced apoptosis was observed in metanephric blastemas of bcl-2 (-/-) embryos.
- In vitro culture demonstrated reduced growth of bcl-2 (-/-) metanephroi.
Conclusions:
- bcl-2 is essential for normal kidney development.
- Absence of bcl-2 leads to increased apoptosis and impaired nephrogenesis.
- bcl-2 deficiency causes abnormal kidney morphology and postnatal renal failure.