Suppression of developmental retinal cell death but not of photoreceptor degeneration in Bax-deficient mice.
Suppression of developmental retinal cell death but not of photoreceptor degeneration in Bax-deficient mice.
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发表时间：
1998-08
影响因子：
4.4
通讯作者：
J. M. Ogilvie;T. Deckwerth;C. Knudson;S. Korsmeyer
中科院分区：
文献类型：
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作者：
J. M. Ogilvie;T. Deckwerth;C. Knudson;S. Korsmeyer
Bax是Bcl 2家族的细胞死亡调节因子，通过促进细胞凋亡诱导细胞死亡。在这项研究中检查了Bax缺陷小鼠，以确定Bax是否是发育中的视网膜细胞死亡和RD突变导致的病理性凋亡性感光细胞变性所必需的。方法取出生后第7天（P）的Wistar小鼠及其野生型同胞视网膜，进行TdT-dUTP末端缺口末端标记（TUNEL）染色，计数含DNA片段的细胞核数。将成人视网膜和视神经处理成塑料包埋的1微米切片，并测定横截面积。突变的Bax等位基因远系繁殖到携带rd等位基因的C3 H小鼠品系上。在大多数感光细胞死亡后的P21，对这些动物的视网膜进行组织学检查。结果在P7时，在内核层（INL）的细胞死亡高峰期，在INL和神经节细胞层（GCL）中，与野生型同胞相比，在缺失型小鼠中TUNEL阳性神经元显著减少。在成年视网膜神经节细胞缺陷小鼠中，视神经的横截面积比野生型同胞大约50%，视网膜神经节细胞轴突总数增加到226%。INL基因缺陷小鼠的INL比正常小鼠厚。Bax基因型不影响野生型或突变型RD等位基因小鼠视网膜外核层的厚度或组织学外观。结论：在Bax基因表达缺失的情况下，视网膜神经节细胞的存活率显著增加，并持续到成年期。类似地，INL细胞的死亡减少但不完全消除。然而，Bax的缺乏并不能保护光感受器免于自然发生的细胞死亡或由rd突变诱导的变性。这表明Bax在不同程度上参与视网膜中发育细胞死亡的控制，并且并非所有凋亡性视网膜细胞死亡都由Bax控制。
PURPOSE Bax, a member of the Bcl2 family of cell death regulators, induces cell death by promoting the induction of apoptosis. Bax-deficient mice were examined in this study to determine whether Bax is required for cell death in the developing retina and for pathologic apoptotic photoreceptor degeneration resulting from the rd mutation. METHODS Retinas from Bax-deficient mice and their wild-type siblings were harvested at postnatal day (P) 7 and processed for TdT-dUTP terminal nick-end labeling (TUNEL) staining, and the number of nuclei containing fragmented DNA were counted. Adult retinas and optic nerves were processed for plastic-embedded 1-microm sections, and the cross-sectional area was determined. The mutant Bax allele was outbred onto the C3H mouse strain, which carries the rd allele. Retinas from these animals were examined histologically at P21 after most of the photoreceptor cell death had occurred. RESULTS At P7, around the time of peak cell death in the inner nuclear layer (INL), significantly fewer neurons in INL and ganglion cell layer (GCL) were TUNEL positive in Bax-deficient mice than in their wild-type siblings. In adult Bax-deficient mice, the cross-sectional area of the optic nerve was approximately 50% larger than in wild-type siblings, and the total number of retinal ganglion cell axons was increased to 226%. The INL of Bax-deficient mice was thicker than normal. The Bax genotype did not affect the thickness or histologic appearance of the outer nuclear layer in retinas of mice with wild-type or mutant rd alleles. CONCLUSIONS In the absence of the expression of the Bax gene, there is a profound increase in the survival of retinal ganglion cells that lasts into adulthood. Similarly, death of INL cells is diminished but not completely abolished. The absence of Bax does not, however, protect photoreceptors from naturally occurring cell death or degeneration induced by the rd mutation. This shows that Bax is involved to a variable degree in the control of developmental cell death in the retina and that not all apoptotic retinal cell deaths are controlled by Bax.