Harrison S M, Roffler-Tarlov S K
Department of Anatomy and Cell Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Dev Biol. 1998 Mar 15;195(2):174-86. doi: 10.1006/dbio.1998.8848.
The murine mutation weaver confers early death during development on cells in testes, cerebellum, and midbrain. The results reported here support the hypothesis that the action of weaver is intrinsic to testes and independent of Sertoli cells: germ cells are the only testicular cell type seen to die in weaver homozygotes, while Sertoli cell-dependent development of the blood testis barrier is normal. This report includes characterization of patterns of germ cell death and cerebellar granule cell death in homozygous weavers with respect to that seen during normal development by in situ end-labeling of DNA and high-magnification light microscopy. Comparison of the spatial distribution of dying cells in the weaver's cerebellum with that of dividing cells revealed disarray in the external germinal zone. The results show that cells vulnerable to weaver die by apoptotic and nonapoptotic mechanisms and indicate that weaver-induced cell death is not the consequence of extended naturally occurring developmental cell death, although their timing overlaps. Thus, although the death of cells in each region is likely to be caused by the same mutation, a base pair substitution in the G protein-coupled inwardly rectifying potassium channel 2 gene, the cell death program activated differs depending on cell type.
小鼠突变体“织工”会导致睾丸、小脑和中脑的细胞在发育过程中过早死亡。本文报道的结果支持这样一种假说：“织工”的作用是睾丸固有的，且独立于支持细胞：生殖细胞是在“织工”纯合子中唯一可见死亡的睾丸细胞类型，而血睾屏障依赖支持细胞的发育是正常的。本报告包括通过DNA原位末端标记和高倍光学显微镜观察，对纯合“织工”小鼠中生殖细胞死亡模式和小脑颗粒细胞死亡模式与正常发育过程中所见模式的特征描述。将“织工”小鼠小脑中死亡细胞的空间分布与分裂细胞的空间分布进行比较，发现外生发区排列紊乱。结果表明，易受“织工”影响的细胞通过凋亡和非凋亡机制死亡，这表明“织工”诱导的细胞死亡不是自然发生的发育性细胞死亡延长的结果，尽管它们的时间有重叠。因此，尽管每个区域的细胞死亡可能由相同的突变引起，即G蛋白偶联内向整流钾通道2基因中的一个碱基对替换，但激活的细胞死亡程序因细胞类型而异。
