The inducible Cre-loxP system provides a useful tool for inducing the selective deletion of genes that are essential for proper development and enables the study of gene functions in properly developed animals. Here, we show that inducible Cre-loxP driven by the Gli1-promoter can induce cell-type-specific deletion of target genes in cerebellar cortical neurons. We used reporter mice containing the YFP (yellow fluorescence protein) gene at the Gt(ROSA)26Sor locus with a loxP-flanked transcriptional stop sequence, in which successful Cre-mediated excision of the stop sequence is indicated by YFP expression in Cre-expressing cells. Administration of tamoxifen during early postnatal days (P4~7) induces Cre-dependent excision of stop sequences and allows YFP expression in proliferating neuronal progenitor cells in the external granule layer and Bergmann glia in the Purkinje cell layer. A substantial number of YFP-positive progenitor cells in the external granule layer migrated to the internal granule cell layer and became granule cell neurons. By comparison, injection of tamoxifen during late postnatal days (P19~22) induces YFP expression only in Bergmann glia, and most granule cell neurons were devoid of YFP expression. The results indicate that the Gli1 promoter is temporarily active in progenitor cells in the external granule layer during the early postnatal period but constitutively active in Bergmann glia. We propose that the Gli1-mediated CreER system can be applied for the conditional deletion of genes of interest from cerebellar granule cell neurons and/or Bergmann glia.

中文翻译：

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在发育中的小脑中使用 Gli1 介导的 Cre 重组进行细胞类型特异性敲除。

诱导型Cre-loxP系统提供了一种有用的工具，用于诱导对正常发育至关重要的基因的选择性缺失，并能够在适当发育的动物中研究基因功能。在这里，我们表明由Gli1启动子驱动的可诱导Cre-loxP可以诱导小脑皮质神经元中靶基因的细胞类型特异性缺失。我们使用在Gt(ROSA)26Sor基因座上含有 YFP（黄色荧光蛋白）基因的报告小鼠和loxP-侧翼转录终止序列，其中，Cre 表达细胞中的 YFP 表达表明 Cre 介导的终止序列的成功切除。在出生后早期 (P4~7) 施用他莫昔芬诱导停止序列的 Cre 依赖性切除，并允许 YFP 在外部颗粒层中增殖的神经元祖细胞和浦肯野细胞层中的 Bergmann 胶质细胞中表达。外部颗粒层中大量 YFP 阳性祖细胞迁移到内部颗粒细胞层并成为颗粒细胞神经元。相比之下，在出生后后期（P19~22）注射他莫昔芬仅在伯格曼神经胶质中诱导 YFP 表达，并且大多数颗粒细胞神经元缺乏 YFP 表达。结果表明，Gli1 启动子在出生后早期在外部颗粒层的祖细胞中暂时活跃，但在 Bergmann 神经胶质中具有组成型活性。我们建议 Gli1 介导的 CreER 系统可用于有条件地删除小脑颗粒细胞神经元和/或 Bergmann 胶质细胞中感兴趣的基因。