Lessons on Conditional Gene Targeting in Mouse Adipose Tissue
Open accessAbstract
Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation. To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter. All three Cre lines demonstrated recombination in the brown and white fat pads. Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat. The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle. In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ∼2% of spermatozoa. Thus, different “adipocyte-specific” Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology.
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Adiponectin-Cre transgenic mice drive Cre expression specifically in adipose tissues.
“Thus, to explore the significance of FGF21 signaling directly to adipose tissues, investigators crossed mice with a conditional Klb allele with Adiponectin-Cre transgenic mice (11), which drive Cre expression specifically in adipose tissues (75).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [75]
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- Authors
- Lee, K. Y., Russell, S. J., Ussar, S., Boucher, J., Vernochet, C., Mori, M. A., Smyth, G., Rourk, M., Cederquist, C., Rosen, E. D., Kahn, B. B., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Kahn, C. Ronald
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-02-14
- Volume
- 62
- Issue
- 3
- Pages
- 864-874
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3581196
- OpenAlex
- W2103370215
- Cited by
- 328
- References
- 52
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 16 · 2023: 19 · 2022: 17 · 2021: 22 · 2020: 23 · 2019: 36 · 2018: 35 · 2017: 34 · 2016: 36 · 2015: 30 · 2014: 33 · 2013: 10
- FWCI
- 25.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031036, R01DK031036, DK 82655, DK-60837, R01DK060837, R01DK043051, T32DK007260, P30DK036836, R01DK082659)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Keywords
- conditional gene targeting, adipose tissue, tamoxifen-inducible Cre, Rosa26 reporter, floxed allele, recombination efficiency, brown adipose tissue, white adipose tissue, skeletal muscle
- MeSH terms
- Adipose Tissue, Animals, Crosses, Genetic, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Promoter Regions, Genetic, Recombinant Fusion Proteins, Recombination, Genetic, Tamoxifen, Viral Proteins, Macrophages, Peritoneal, Mice, Knockout, Transgenes, Integrases, Fatty Acid-Binding Proteins, Mice, Adiponectin
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