Evidence for baseline retinal pigment epithelium pathology in the Trp1-Cre mouse

Aristomenis Thanos, Yuki Morizane, Yusuke Murakami, Andrea Giani, Dimosthenis Mantopoulos, Maki Kayama, Mi In Roh, Norman Michaud, Basil Pawlyk, Michael Sandberg, Lucy H. Young, Joan W. Miller, Demetrios G. Vavvas

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies.

Original languageEnglish
Pages (from-to)1917-1927
Number of pages11
JournalAmerican Journal of Pathology
Volume180
Issue number5
DOIs
Publication statusPublished - May 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Thanos, A., Morizane, Y., Murakami, Y., Giani, A., Mantopoulos, D., Kayama, M., Roh, M. I., Michaud, N., Pawlyk, B., Sandberg, M., Young, L. H., Miller, J. W., & Vavvas, D. G. (2012). Evidence for baseline retinal pigment epithelium pathology in the Trp1-Cre mouse. American Journal of Pathology, 180(5), 1917-1927. https://doi.org/10.1016/j.ajpath.2012.01.017