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 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.
Nagata
M
M
Department of Pathology, University of Tsukuba, Japan.
Nakauchi
H
H
Nakayama
K
K
Nakayama
K
K
Loh
D
D
Watanabe
T
T
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D005260:Female; D006579:Heterozygote; D007668:Kidney / Q000737:chemistry / Q000196:embryology / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009399:Nephrons / Q000196:embryology* / Q000254:growth & development / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D013234:Stem Cells / Q000737:chemistry / Q000473:pathology / Q000502:physiology
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA