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Metabolic phenotypes in a Lyz2Cre recombinase mouse model.

S M Niazur Rahman¹, Justin Hou Ming Yung¹, Allen Volchuk²

¹Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Frontiers in Immunology

|April 2, 2025

Summary

Cre recombinase expression can affect glucose metabolism, even without gene deletion. This study emphasizes the need for Cre-only controls in conditional knockout mouse models to ensure accurate research findings.

Keywords:

Cre-Lox P system Lyz2Cre glucose metabolism insulin resistance macrophage obesity-associated diabetes β-cell dysfunction

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Published on: November 20, 2018

Area of Science:

Molecular Biology
Immunology
Metabolic Research

Background:

The Cre-lox system enables precise gene deletion in specific cell types for disease research.
Cre recombinase expression is generally considered safe but may cause toxicity or unintended gene disruption.

Purpose of the Study:

To investigate the role of macrophage nucleotide-binding oligomerization domain (Nod1) in obesity-associated diabetes.
To evaluate the impact of Cre recombinase expression alone on glucose metabolism.

Main Methods:

Utilized myeloid-specific Nod1-knockout mice (Nod1 floxed crossed with Lyz2Cre).
Separately analyzed Lyz2Cre and floxed control mice to isolate Cre effects.

Main Results:

Lyz2Cre expression alone significantly impacted glucose metabolism.
This finding challenges the assumption that Cre expression is benign in conditional knockout studies.

Conclusions:

Cre-only control groups are essential for validating results from floxed allele-based conditional knockout mouse models.
Ensuring Cre-only controls is critical for robust and accurate conclusions in molecular and genetic research.