Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination
Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination
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DOI：
10.1128/mcb.24.17.7636-7642.2004
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发表时间：
2004-09-01
影响因子：
5.3
通讯作者：
Riethmacher, D
中科院分区：
文献类型：
--
作者：
Brockschnieder, D;Lappe-Siefke, C;Riethmacher, D
异常细胞损失是大量发育和退行性疾病的常见原因。为了在转基因动物中模拟这种疾病，我们已经开发了一种小鼠品系，其允许在体细胞Cre介导的基因重组后在体内有效耗尽几乎任何细胞类型。通过将白喉毒素片段A（DT-A）基因作为条件表达构建体（floxed lacZ-DT-A）引入到遍在表达的ROSA 26位点中，我们产生了允许毒素基因的细胞特异性激活的小鼠品系。在细胞类型特异性启动子控制下的Cre介导的重组后，lacZ基因表达被Cre重组DT-A基因的从头转录有效地取代。我们提供了这一原理的证据，最初用于中枢神经系统（锥体神经元和少突胶质细胞）、免疫系统（B细胞）和肝组织（肝细胞）的细胞，DT-A的条件表达在体内是功能性的，导致产生新的退行性疾病模型。
Abnormal cell loss is the common cause of a large number of developmental and degenerative diseases. To model such diseases in transgenic animals, we have developed a line of mice that allows the efficient depletion of virtually any cell type in vivo following somatic Cre-mediated gene recombination. By introducing the diphtheria toxin fragment A (DT-A) gene as a conditional expression construct (floxed lacZ-DT-A) into the ubiquitously expressed ROSA26 locus, we produced a line of mice that would permit cell-specific activation of the toxin gene. Following Cre-mediated recombination under the control of cell-type-specific promoters, lacZ gene expression was efficiently replaced by de novo, transcription of the Cre-recombined DT-A gene. We provide proof of this principle, initially for cells of the central nervous system (pyramidal neurons and oligodendrocytes), the immune system (B cells), and liver tissue (hepatocytes), that the conditional expression of DT-A is functional in vivo, resulting in the generation of novel degenerative disease models.