Generation of Cre Transgenic Mice with Postnatal RPE-Specific Ocular Expression
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PURPOSE: To generate and characterize a constitutively active, RPE-specific, cre-expressing transgenic mouse line. This line can be used to create RPE-specific knockouts by crossing with mice harboring loxP-flanked (floxed) genes. METHODS: A transgene construct was assembled with the BEST1 promoter driving cre expression. Transgenic mice were generated on a C57BL/6 background. Cre expression was assessed by immunofluorescence and Western blot analysis. Cre enzymatic activity was tested by crossing to three lines with floxed DNA regions and detecting deletion of the intervening sequences or through histochemical detection of lacZ activity. Potential cre-mediated toxicity was assessed by retinal histology up to 24 months of age and by electroretinography. RESULTS: The BEST1-cre line with expression in the highest percentage of RPE cells displayed a patchy mosaic expression pattern, with 50% to 90% of RPE cells expressing cre. In mice outcrossed to a mixed B6/129 background, expression was consistently found in 90% of RPE cells. Within the eye, only the RPE cells were immunoreactive with an anti-cre antibody. Maximum cre expression quantified by Western blot analysis occurred at P28. Crosses with three lines containing floxed sequences revealed RPE-specific cre activity in the eye and extraocular expression limited to the testes. Histology and electroretinography showed no cre-mediated RPE toxicity. CONCLUSIONS: This BEST1-cre transgenic line enables generation of RPE-specific knockout mice. The mosaic expression pattern provides an internal control; the non-cre-expressing RPE cells continue to express the floxed genes. These mice should facilitate study of the multifunctional RPE and the generation of mouse models of human retinal disease.
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The Best1 promoter provides RPE-specific expression of Cre-recombinase and RPE-selective loss of a loxP-flanked gene.
“Recently, Dunaief and coworkers described a mouse strain in which the Best1 promoter was used to provide RPE-specific expression of the Crerecombinase and RPE-selective loss of a loxP-flanked gene. 34”
From Deletion of autophagy inducer <i>RB1CC1</i> results in degeneration of the retinal pigment epithelium (2015) · cites this paper as [34]
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- Authors
- Iacovelli, J., Zhao, C., Wolkow, N., Veldman, P., Gollomp, K., Ojha, P., Lukinova, N., King, A., Feiner, L., Esumi, N., Zack, D. J., Pierce, E. A., Vollrath, D., & Dunaief, J. L.
- Affiliations
- University of Pennsylvania (US)
- Stanford Medicine (US)
- Johns Hopkins University (US)
- ORCID
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2011-03-14
- Volume
- 52
- Issue
- 3
- Pages
- 1378
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3101664
- OpenAlex
- W2034940836
- Cited by
- 89
- References
- 27
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 13 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 4
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Health Assistance Foundation
- Foundation Fighting Blindness
- University of Pennsylvania
- Edward N. and Della L. Thome Memorial Foundation
- Retina Research Foundation
- National Institutes of Health
- National Institute on Aging (F30AG037289)
- National Eye Institute (EY 015240, T-32 EY007035-30, EY12910, R03EY014650, T32EY007035, R01EY015240, R01EY012910, EY014650)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Keywords
- retinal pigment epithelium, transgenic mouse lines, mosaic expression, electroretinogram
- MeSH terms
- Bestrophins, Animals, Electroretinography, Eye Proteins, Female, Ion Channels, Mice, Inbred C57BL, Mice, Transgenic, Promoter Regions, Genetic, Blotting, Western, Gene Expression Regulation, Enzymologic, Polymerase Chain Reaction, Fluorescent Antibody Technique, Indirect, Integrases, Mice, Retinal Pigment Epithelium
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