Metabolic phenotype in the Lyz2Cre recombinase mouse model

S M Niazur Rahman ¹ Justin Hou Ming Yung ¹ Adria Giacca ^1,2,3,4*

• ¹ Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
• ² Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
• ³ Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
• ⁴ Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

The Cre-Lox system is essential in biomedical research for precise gene deletion in specific cell types, crucial for understanding genetic roles in disease. Although generally considered nondetrimental, Cre recombinase expression has been associated with potential adverse effects, including Cre toxicity, ectopic expression, and disruption of endogenous genes. We investigated the role of macrophage Nod1 in obesity-associated diabetes using myeloid-specific Nod1knockout mice (Nod1 floxed crossed with Lyz2Cre). Our study examined Lyz2Cre effects independently, unlike most research pooling floxed and Cre control mice. Results indicated Lyz2Cre expression alone impacts glucose metabolism, challenging the notion that Cre expression is harmless. This finding highlights the critical importance of including Cre-only controls in studies using floxed alleles to generate conditional knockout mouse models, in order to ensure robust and accurate conclusions in molecular research.