APOPTOSIS DURING AN EARLY-STAGE OF NEPHROGENESIS INDUCES RENAL HYPOPLASIA IN BCL-2-DEFICIENT MICE

Renal development in bcl-2-deficient mice was monitored to examine the temporal and spatial function of this gene during nephrogenesis in vi va Extensive apoptosis occurred during abnormal nephrogenesis in bcl-2 -deficient mice. In embryos and newborn mice, the sequence of morpholo gical events was monitored by morphology in conjunction with morphomet ry, and bcl-2 -/-, bcl-2 +/-, and bcl-2 +/+ mice were compared, In bcl -2 -/- mice, initial induction of nephrons was detected by embryonic d ay 13 (E-13) as normal. Then, apoptotic cells became five times more f requent at E-13 to E-16 with a significant reduction (1/5) in nephron number at E-17 to E-13 in bcl-2 -/- mice compared with bcl-2 +/+ mice, No morphological difference was evident between bcl-2 +/- mice and bc l-2 +/+ mice by morphometry. Apoptotic cells were found mainly among t he mesenchyme and less frequently in tubuli, Little apoptosis among ur eteric buds was noted. In bcl-2 -/- mice at E-17 to E-19, inactive bra nching and insufficient convolution of ureteric buds were accompanied by fulminant apoptosis in the mesenchyme. Neonatal bcl-2 -/- mice lack ed the nephrogenic rone, exhibiting renal hypoplasia. Thus, bcl-2 seem s to inhibit apoptosis in renal stem cells during the induction of nep hrons in vivo.