Teratogen-induced eye defects mediated by p53-dependent apoptosis.
Teratogen-induced eye defects mediated by p53-dependent apoptosis.
复制标题
由 p53 依赖性细胞凋亡介导的致畸诱导的眼部缺陷。
DOI：
10.1016/s0960-9822(02)00422-0
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Knudsen,TB
中科院分区：
文献类型：
--
作者：
Wubah,JA;Ibrahim,MM;Gao,X;Nguyen,D;Pisano,MM;Knudsen,TB
Background:Many birth defects are believed to involve gene–environment interactions, although the mechanisms involved are poorly understood. Apoptosis is a common effect of many kinds of environmental stresses on the developing embryo; therefore, mechanisms of teratogenesis may be approached within the context of the cell death program. Thep53tumor suppressor gene encodes a transcription factor which functions as a critical regulator of apoptosis in response to environmental stress.ResultsTo investigate the relationship betweenp53-dependent apoptosis and teratogenesis, we subjected day 8 mouse embryos with differentp53gene backgrounds to a genotoxic stress, 2-chloro-2′-deoxyadenosine. Treatment rapidly stimulated nuclear p53 accumulation and triggered apoptosis in some (head-fold) but not other (primitive heart) developing structures. Induced cell death wasp53gene-dose dependent, as shown by the intermediate sensitivity of 4–5 somite stage embryos bearing only a single effectivep53allele and the lack of sensitivity ofp53-null mutants. Abnormal development was manifested as eye defects by day 11, particularly lens agenesis. Overall the incidences of these defects at term were 73.3 % forp53wild-type fetuses, 52.5 % for heterozygous mutants, and 2.2 % forp53-null mutants. Statistical analysis indicated that the interaction between teratogen and genotype was highly significant (P ≤ 0.001) for cell death on day 8 and eye defects on day 17.ConclusionWe conclude that teratogen induction ofp53-dependent apoptosis in the developing embryo is positively coupled to the determination of congenital eye defects.
