THYMIDINE KINASE OBLITERATION - CREATION OF TRANSGENIC MICE WITH CONTROLLED IMMUNE-DEFICIENCY
THYMIDINE KINASE OBLITERATION - CREATION OF TRANSGENIC MICE WITH CONTROLLED IMMUNE-DEFICIENCY
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DOI：
10.1073/pnas.86.8.2698
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发表时间：
1989-04-01
影响因子：
11.1
通讯作者：
EVANS, RM
中科院分区：
文献类型：
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作者：
HEYMAN, RA;BORRELLI, E;EVANS, RM
单纯疱疹病毒1型胸苷激酶（HSV-1-tk）的细胞特异性表达为转基因小鼠中实现靶细胞类型的条件性消融提供了简单高效的技术。通过用抗疱疹药物更昔洛韦治疗表达HSV-1-tk的转基因动物来诱导消融。在从免疫球蛋白启动子表达HSV-1-tk的小鼠淋巴组织中，给予更昔洛韦导致B细胞和T细胞谱系的大量破坏。不表达HSV-1-tk的组织对药物治疗不敏感。在消耗> 99%的总胸腺细胞后，保留了许多祖细胞，其能够在7天内重新填充所有T细胞谱系。控制和直接消融的能力允许在精确的发育时期产生条件突变体表型。该技术还提供了一种潜在的手段，以丰富干细胞群，以及允许创建特定病理条件的动物模型。
The cell-specific expression of herpes simplex virus 1 thymidine kinase (HSV-1-tk) has provided a simple and highly efficient technique to achieve conditional ablation of targeted cell types in transgenic mice. The ablation is induced by treating transgenic animals expressing HSV-1-tk with the antiherpetic drug ganciclovir. In lymphoid tissue of mice expressing HSV-1-tk from an immunoglobulin promoter, administration ganciclovir leads to massive destruction of B- and T-cell lineages. Tissues not expressing HSV-1-tk are insensitive to drug treatment. After depletion of > 99% of total thymocytes, a number of progenitor cells remain that are able to repopulate all T-cell lineages within 7 days. The ability to control and direct ablation allows for creation of conditional mutant phenotypes at precise periods of development. This technique also provides a potential means to enrich stem cell populations as well as permitting the creation of animal models for particular pathological conditions.