Cited by 328Adipose Tissue and MetabolismCRISPR and Genetic EngineeringAnimal Genetics and Reproduction

Lessons on Conditional Gene Targeting in Mouse Adipose Tissue

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Lee, Kevin Y., Russell, Steven J., Ussar, Siegfried, Boucher, Jeremie, Vernochet, Cecile, Mori, Marcelo A., Smyth, Graham, Rourk, Michael +4 more·2013·Diabetes

Abstract

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).”

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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
Venue
Diabetes
Published
2013-02-14
Volume
62
Issue
3
Pages
864-874
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
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
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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