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两种新型的 CreER 转基因小鼠品系可用于研究体内黑素细胞。

Two novel CreER transgenic mouse lines to study melanocytic cells in vivo.

机构信息

Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.

Faculty of Computer Science, Deggendorf Institute of Technology, Deggendorf, Germany.

出版信息

Pigment Cell Melanoma Res. 2022 Nov;35(6):613-621. doi: 10.1111/pcmr.13061. Epub 2022 Aug 15.

DOI:10.1111/pcmr.13061
PMID:35920064
Abstract

The skin of adult mammals protects from radiation, physical and chemical insults. While melanocytes and melanocyte-producing stem cells contribute to proper skin function in healthy organisms, dysfunction of these cells can lead to the generation of malignant melanoma-the deadliest type of skin cancer. Addressing cells of the melanocyte lineage in vivo represents a prerequisite for the understanding of melanoma on cellular level and the development of preventive and treatment strategies. Here, the inducible Cre-loxP-system has emerged as a promising tool to specifically target, monitor, and modulate cells in adult mice. Re-analysis of existing sequencing data sets of melanocytic cells revealed that genes with a known function in neural cells, including neural stem cells (Aldh1L1 and Nestin), are also expressed in melanocytic cells. Therefore, in this study, we explored whether the promoter activity of Nestin and Aldh1L1 can serve to target cells of the melanocyte lineage using the inducible CreER -loxP-system. Using an immunohistochemical approach and different time points of analysis, we were able to map the melanocytic fate of recombined stem cells in the adult hair follicle of Nestin-CreER and Aldh1L1-CreER transgenic mice. Thus, we here present two new mouse models and propose their use to study and putatively modulate adult melanocytic cells in vivo.

摘要

成年哺乳动物的皮肤可以抵御辐射、物理和化学刺激。虽然黑素细胞和黑素细胞产生的干细胞有助于健康生物的皮肤正常功能,但这些细胞的功能障碍会导致恶性黑色素瘤的产生——这是最致命的皮肤癌类型。在体内研究黑素细胞谱系的细胞是理解黑色素瘤在细胞水平上的作用以及制定预防和治疗策略的前提。在这里,诱导型 Cre-loxP 系统已成为一种有前途的工具,可以特异性地靶向、监测和调节成年小鼠中的细胞。对黑素细胞的现有测序数据集的重新分析表明,已知在神经细胞(包括神经干细胞(Aldh1L1 和 Nestin))中具有功能的基因也在黑素细胞中表达。因此,在这项研究中,我们使用诱导型 CreER-loxP 系统探索了 Nestin 和 Aldh1L1 的启动子活性是否可以用于靶向黑素细胞谱系的细胞。通过免疫组织化学方法和不同的分析时间点,我们能够在 Nestin-CreER 和 Aldh1L1-CreER 转基因小鼠的成年毛囊中追踪重组干细胞的黑素细胞命运。因此,我们在这里提出了两种新的小鼠模型,并建议将其用于研究和潜在地在体内调节成年黑素细胞。

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Two novel CreER transgenic mouse lines to study melanocytic cells in vivo.两种新型的 CreER 转基因小鼠品系可用于研究体内黑素细胞。
Pigment Cell Melanoma Res. 2022 Nov;35(6):613-621. doi: 10.1111/pcmr.13061. Epub 2022 Aug 15.
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Methods Mol Biol. 2019;2045:187-199. doi: 10.1007/7651_2019_214.
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Specificity and efficiency of reporter expression in adult neural progenitors vary substantially among nestin-CreER(T2) lines.在成年神经祖细胞中,报告基因表达的特异性和效率在巢蛋白-CreER(T2)品系之间存在显著差异。
J Comp Neurol. 2014 Apr 1;522(5):1191-208. doi: 10.1002/cne.23497.
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Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines.差异型星形胶质细胞特异性启动子驱动的诱导型 Cre 重组酶在转基因小鼠品系中的表达模式。
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In vivo contribution of nestin- and GLAST-lineage cells to adult hippocampal neurogenesis.巢蛋白和 GLAST 谱系细胞对成年海马神经发生的体内贡献。
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Sequencing two Tyr::CreER transgenic mouse lines.测序两个 Tyr::CreER 转基因鼠系。
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High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly.神经祖细胞中高水平的Cre表达会导致大脑发育缺陷,进而引发小头畸形和脑积水。
J Neurosci. 2006 Sep 13;26(37):9593-602. doi: 10.1523/JNEUROSCI.2815-06.2006.

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