Rahman S M Niazur, Yung Justin Hou Ming, Volchuk Allen, Goldenberg Neil M, Giacca Adria
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Front Immunol. 2025 Mar 18;16:1499858. doi: 10.3389/fimmu.2025.1499858. eCollection 2025.
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 non-detrimental, 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 nucleotide-binding oligomerization domain (Nod1) in obesity-associated diabetes using myeloid-specific Nod1-knockout mice (Nod1 floxed crossed with Lyz2Cre). Our study examined Lyz2Cre as well as floxed control mice separately, unlike most research. Results indicated that 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.
Cre-Lox系统在生物医学研究中对于特定细胞类型的精确基因缺失至关重要,这对于理解疾病中的基因作用至关重要。尽管通常认为无害,但Cre重组酶的表达与潜在的不良反应有关,包括Cre毒性、异位表达和内源基因的破坏。我们使用髓系特异性Nod1基因敲除小鼠(Nod1基因 floxed 与Lyz2Cre杂交)研究了巨噬细胞核苷酸结合寡聚化结构域(Nod1)在肥胖相关糖尿病中的作用。与大多数研究不同,我们的研究分别检查了Lyz2Cre以及floxed对照小鼠。结果表明,单独的Lyz2Cre表达会影响葡萄糖代谢,这对Cre表达无害的观点提出了挑战。这一发现凸显了在使用floxed等位基因生成条件性敲除小鼠模型的研究中纳入仅含Cre的对照的至关重要性,以便在分子研究中确保得出可靠且准确的结论。