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

Skeletal muscle-specific Cre recombinase expression, controlled by the human α-skeletal actin... 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 ob- served 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetologia Springer Journals

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

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Medicine & Public Health; Internal Medicine; Metabolic Diseases; Human Physiology
ISSN
0012-186X
eISSN
1432-0428
D.O.I.
10.1007/s00125-018-4643-x
Publisher site
See Article on Publisher Site

Abstract

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 ob- served 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

Journal

DiabetologiaSpringer Journals

Published: Jun 1, 2018

References

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