Cre重组酶：有它不行，没它也不行。

Cre Recombinase: You Can't Live with It, and You Can't Live Without It.

作者信息

Le Yun-Zheng, Zhu Meili, Anderson Robert E

机构信息

Departments of Medicine Endocrinology and Cell Biology, and Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, 941 S. L. Young Blvd., BSEB 302G, 73104, Oklahoma City, OK, USA.

Department of Medicine Endocrinology, University of Oklahoma Health Sciences Center, 73104, Oklahoma City, OK, USA.

出版信息

Adv Exp Med Biol. 2016;854:725-30. doi: 10.1007/978-3-319-17121-0_96.

DOI:10.1007/978-3-319-17121-0_96

PMID:26427481

Abstract

The development of conditional gene targeting has greatly advanced our knowledge of human retinal diseases, but issues have arisen related to the use of some Cre-expressing mouse lines. In this article, we discuss potential problems associated with transgenic Cre expression-induced degeneration and alteration of rod photoreceptors and retinal pigment epithelium (RPE). Our strategy for circumventing RPE degeneration by induced transient Cre expression uses a single intravitreal doxycycline injection in a tetracycline-inducible RPE-specific Cre mouse line, which results in productive Cre-mediated recombination efficiently in the RPE. As constitutive expression of Cre in the RPE alters RPE biology, this inducible Cre/lox system provides an opportunity for conditional gene targeting in the RPE, a tissue that is closely related to photoreceptor degeneration, age-related macular degeneration, and diabetic retinopathy.

摘要

条件性基因打靶技术的发展极大地推进了我们对人类视网膜疾病的认识，但在使用某些表达Cre的小鼠品系时出现了一些问题。在本文中，我们讨论了与转基因Cre表达诱导的视杆光感受器和视网膜色素上皮（RPE）变性及改变相关的潜在问题。我们通过诱导短暂表达Cre来规避RPE变性的策略是，在四环素诱导的RPE特异性Cre小鼠品系中进行单次玻璃体内强力霉素注射，这会在RPE中高效地产生Cre介导的重组。由于Cre在RPE中的组成型表达会改变RPE生物学特性，这种诱导型Cre/lox系统为在RPE中进行条件性基因打靶提供了机会，RPE是一种与光感受器变性、年龄相关性黄斑变性和糖尿病性视网膜病变密切相关的组织。