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Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Published on: April 27, 2017
Ectopic recombination in the central and peripheral nervous system by aP2/FABP4-Cre mice: implications for metabolism
Katrin Martens1, Astrid Bottelbergs, Myriam Baes
1Laboratory of Cell Metabolism, Department of Pharmaceutical Sciences, K.U. Leuven, Leuven, Belgium.
Abstract:
aP2-Cre mice have amply been used to generate conditional adipose selective inactivation of important signaling molecules. We show that the efficiency of Cre mediated recombination in adipocytes and adipose selectivity is not always guaranteed. In particular, Cre activity was found in ganglia of the peripheral nervous system (PNS), in adrenal medulla and in neurons throughout the central nervous system (CNS). Because these tissues have an important impact on adipose tissue, care should be taken when using aP2-Cre mice to define the role of the targeted genes in adipose tissue function.
Insights
aP2-Cre mice show unreliable Cre recombination in fat cells. Cre activity is also detected in the nervous system and adrenal medulla, impacting adipose tissue studies.
Area of Science:
- Metabolism and Endocrinology
- Genetics and Genomics
- Neuroscience
Background:
- Adipose-specific gene inactivation is crucial for understanding metabolic signaling.
- aP2-Cre mouse models are widely used for conditional gene targeting in adipocytes.
Purpose of the Study:
- To evaluate the adipose selectivity and efficiency of Cre-mediated recombination in aP2-Cre mice.
- To identify potential off-target sites of Cre activity in aP2-Cre models.
Main Methods:
- Utilized aP2-Cre mouse model to assess Cre-mediated recombination.
- Analyzed Cre activity in various tissues including adipose tissue, peripheral nervous system (PNS), central nervous system (CNS), and adrenal medulla.
Main Results:
- Demonstrated that Cre-mediated recombination in adipocytes is not consistently efficient or adipose-selective.
- Detected significant Cre activity in PNS ganglia, adrenal medulla, and CNS neurons.
- Highlighted the potential for confounding results due to Cre expression in non-adipose tissues.
Conclusions:
- Caution is advised when using aP2-Cre mice for studying adipose tissue function due to observed Cre activity in the nervous system and adrenal medulla.
- The findings necessitate careful experimental design and interpretation when employing aP2-Cre models to avoid misattributing gene functions.
