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. 1996 May;148(5):1601–1611.

Apoptosis during an early stage of nephrogenesis induces renal hypoplasia in bcl-2-deficient mice.

M Nagata 1, H Nakauchi 1, K Nakayama 1, K Nakayama 1, D Loh 1, T Watanabe 1
PMCID: PMC1861554  PMID: 8623928

Abstract

Renal development in bcl-2-deficient mice was monitored to examine the temporal and spatial function of this gene during nephrogenesis in vivo. Extensive apoptosis occurred during abnormal nephrogenesis in bcl-2-deficient mice. In embryos and newborn mice, the sequence of morphological events was monitored by morphology in conjunction with morphometry, and bcl-2 -/-, bcl-2 +/-, and bcl-2 +/+ mice were compared. In bcl-2 -/- mice, initial induction of nephrons was detected by embryonic day 13 (E-13) as normal. Then, apoptotic cells became five times more frequent at E-13 to E-16 with a significant reduction (1/5) in nephron number at E-17 to E-19 in bcl-2 -/- mice compared with bcl-2 +/+ mice. No morphological difference was evident between bcl-2 +/- mice and bcl-2 +/+ mice by morphometry. Apoptotic cells were found mainly among the mesenchyme and less frequently in tubuli. Little apoptosis among ureteric buds was noted. In bcl-2 -/- mice at E-17 to E-19, inactive branching and insufficient convolution of ureteric buds were accompanied by fulminant apoptosis in the mesenchyme. Neonatal bcl-2 -/- mice lacked the nephrogenic zone, exhibiting renal hypoplasia. Thus, bcl-2 seems to inhibit apoptosis in renal stem cells during the induction of nephrons in vivo.

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