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Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet.

Publication ,  Journal Article
Al Batran, R; Gopal, K; Martin, MD; Ho, KL; Almutairi, M; Aburasayn, H; Eaton, F; Campbell, JE; Ussher, JR
Published in: Diabetologia
August 2018

AIMS/HYPOTHESIS: Cre-loxP systems are frequently used in mouse genetics as research tools for studying tissue-specific functions of numerous genes/proteins. However, the expression of Cre recombinase in a tissue-specific manner often produces undesirable changes in mouse biology that can confound data interpretation when using these tools to generate tissue-specific gene knockout mice. Our objective was to characterise the actions of Cre recombinase in skeletal muscle, and we anticipated that skeletal muscle-specific Cre recombinase expression driven by the human α-skeletal actin (HSA) promoter would influence glucose homeostasis. METHODS: Eight-week-old HSA-Cre expressing mice and their wild-type littermates were fed a low- or high-fat diet for 12 weeks. Glucose homeostasis (glucose/insulin tolerance testing) and whole-body energy metabolism (indirect calorimetry) were assessed. We also measured circulating insulin levels and the muscle expression of key regulators of energy metabolism. RESULTS: Whereas tamoxifen-treated HSA-Cre mice fed a low-fat diet exhibited no alterations in glucose homeostasis, we observed marked improvements in glucose tolerance in tamoxifen-treated, but not corn-oil-treated, HSA-Cre mice fed a high-fat diet vs their wild-type littermates. Moreover, Cre dissociation from heat shock protein 90 and translocation to the nucleus was only seen following tamoxifen treatment. These improvements in glucose tolerance were not due to improvements in insulin sensitivity/signalling or enhanced energy metabolism, but appeared to stem from increases in circulating insulin. CONCLUSIONS/INTERPRETATION: The intrinsic glycaemia phenotype in the HSA-Cre mouse necessitates the use of HSA-Cre controls, treated with tamoxifen, when using Cre-loxP models to investigate skeletal muscle-specific gene/protein function and glucose homeostasis.

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Published In

Diabetologia

DOI

EISSN

1432-0428

Publication Date

August 2018

Volume

61

Issue

8

Start / End Page

1849 / 1855

Location

Germany

Related Subject Headings

  • Triglycerides
  • Promoter Regions, Genetic
  • Phenotype
  • Muscle, Skeletal
  • Mice, Inbred C57BL
  • Mice
  • Integrases
  • Insulin Resistance
  • Insulin
  • Humans
 

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Al Batran, R., Gopal, K., Martin, M. D., Ho, K. L., Almutairi, M., Aburasayn, H., … Ussher, J. R. (2018). Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet. Diabetologia, 61(8), 1849–1855. https://doi.org/10.1007/s00125-018-4643-x
Al Batran, Rami, Keshav Gopal, Mackenzie D. Martin, Kim L. Ho, Malak Almutairi, Hanin Aburasayn, Farah Eaton, Jonathan E. Campbell, and John R. Ussher. “Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet.Diabetologia 61, no. 8 (August 2018): 1849–55. https://doi.org/10.1007/s00125-018-4643-x.
Al Batran R, Gopal K, Martin MD, Ho KL, Almutairi M, Aburasayn H, et al. Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet. Diabetologia. 2018 Aug;61(8):1849–55.
Al Batran, Rami, et al. “Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet.Diabetologia, vol. 61, no. 8, Aug. 2018, pp. 1849–55. Pubmed, doi:10.1007/s00125-018-4643-x.
Al Batran R, Gopal K, Martin MD, Ho KL, Almutairi M, Aburasayn H, Eaton F, Campbell JE, Ussher JR. Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin promoter, improves glucose tolerance in mice fed a high-fat diet. Diabetologia. 2018 Aug;61(8):1849–1855.
Journal cover image

Published In

Diabetologia

DOI

EISSN

1432-0428

Publication Date

August 2018

Volume

61

Issue

8

Start / End Page

1849 / 1855

Location

Germany

Related Subject Headings

  • Triglycerides
  • Promoter Regions, Genetic
  • Phenotype
  • Muscle, Skeletal
  • Mice, Inbred C57BL
  • Mice
  • Integrases
  • Insulin Resistance
  • Insulin
  • Humans