TARGETED DISRUPTION OF BCL-2-ALPHA-BETA IN MICE - OCCURRENCE OF GRAY HAIR, POLYCYSTIC KIDNEY-DISEASE, AND LYMPHOCYTOPENIA
TARGETED DISRUPTION OF BCL-2-ALPHA-BETA IN MICE - OCCURRENCE OF GRAY HAIR, POLYCYSTIC KIDNEY-DISEASE, AND LYMPHOCYTOPENIA
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DOI：
10.1073/pnas.91.9.3700
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发表时间：
1994-04-26
影响因子：
11.1
通讯作者：
LOH, DY
中科院分区：
文献类型：
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作者：
NAKAYAMA, K;NAKAYAMA, K;LOH, DY
已经制备了携带 bcl-2 α 和 bcl-2 β 转录本的被消融编码区的小鼠。 bcl-2(-)/(-) 突变体较小但具有活力，尽管其中大约一半在 6 周龄时死亡。正如之前在体细胞 bcl-2 基因靶向小鼠中所显示的，出生后几周内淋巴细胞数量显着减少，而其他造血谱系不受影响。在淋巴细胞中，CD8+T细胞消失最快，其次是CD4+T细胞，而B细胞受影响最小。然而，bcl-2(-)/(-)淋巴细胞可以正常响应各种刺激，包括抗CD3、Con A、佛波醇12-肉豆蔻酸酯13-乙酸酯加离子霉素、白细胞介素2、脂多糖和抗IgM抗体。非淋巴器官的异常包括耳廓变小、4-5周龄时毛发颜色变灰以及肾小管出现类似多囊肾病的变化。这些结果表明，Bcl-2 可能参与形态发生过程，其中上皮和间质之间的诱导相互作用很重要，例如在肾脏、毛囊和耳廓软骨膜中。令人惊讶的是，尽管正常小鼠的神经系统、肠道和皮肤表现出高水平的内源性 Bcl-2 表达，但这些器官却表现正常。
Mice carrying ablated coding regions of the bcl-2 alpha and bcl-2 beta transcripts have been made. bcl-2(-)/(-) mutants are smaller but viable, although about half of them die by 6 weeks of age. As shown earlier with somatic bcl-2 gene-targeted mice, the number of lymphocytes markedly decreased within few weeks after birth while other hematopoietic lineages remained unaffected. Among lymphocytes, CD8(+) T cells disappeared most quickly followed by CD4(+) T cells, whereas B cells were least affected. bcl-2(-)/(-) lymphocytes, however, could respond normally to various stimuli including anti-CD3, Con A, phorbol 12-myristate 13-acetate plus ionomycin, interleukin 2, lipopolysaccharide, and anti-IgM antibody. Abnormalities among nonlymphoid organs include smaller auricles, hair color turning gray at 4-5 weeks of age, and polycystic kidney disease-like change of renal tubules. These results suggest that Bcl-2 may be involved during morphogenesis where inductive interactions between epithelium and mesenchyme are important such as in the kidneys, hair follicles, and perichondrium of auricles. Surprisingly, the nervous system, intestines, and skin appear normal despite the fact that these organs show high levels of endogeneous Bcl-2 expression in normal mice.