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Updated: May 16, 2026
An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods
Shannon E Mullican1, Takuya Tomaru, Christine A Gaddis
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Abstract:
Adipose-specific gene deletion in mice is crucial in determining gene function in adipocyte homeostasis and the development of obesity. We noted 100% mortality when the Hdac3 gene was conditionally deleted using Fabp4-Cre mice, the most commonly used model of adipose-targeted Cre recombinase. However, this surprising result was not reproduced using other models of adipose targeting of Cre, including a novel Retn-Cre mouse. These findings underscore the need for caution when interpreting data obtained using Fabp4-Cre mice and should encourage the use of additional or alternative adipose-targeting Cre mouse models before drawing conclusions about in vivo adipocyte-specific functions.
Insights
Conditional gene deletion in mice is key for studying fat cell function. Using Fabp4-Cre mice for Hdac3 deletion led to unexpected mortality, highlighting the need for caution and alternative models in adipocyte research.
Area of Science:
- Metabolic research
- Genetics
- Mouse models
Background:
- Adipose-specific gene deletion is vital for understanding adipocyte function and obesity development.
- The Fabp4-Cre mouse model is widely used for adipose-targeted gene manipulation.
Purpose of the Study:
- To investigate the function of the Hdac3 gene in adipocyte homeostasis.
- To evaluate the reliability of the Fabp4-Cre mouse model for adipose-specific gene deletion.
Main Methods:
- Conditional deletion of the Hdac3 gene in adipose tissue using Cre-lox technology.
- Comparison of results between Fabp4-Cre and Retn-Cre mouse models.
Main Results:
- Complete mortality was observed when Hdac3 was deleted using Fabp4-Cre mice.
- This lethal outcome was not replicated using the Retn-Cre mouse model or other adipose-targeting Cre models.
Conclusions:
- The Fabp4-Cre mouse model may yield misleading results due to off-target effects or toxicity.
- Researchers should exercise caution and utilize multiple adipose-targeting Cre models to validate findings on adipocyte-specific gene function.
