Metabolic phenotypes in a Lyz2Cre recombinase mouse model

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 tox...

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Main Authors: S. M. Niazur Rahman, Justin Hou Ming Yung, Allen Volchuk, Neil M. Goldenberg, Adria Giacca
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499858/full
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author S. M. Niazur Rahman
Justin Hou Ming Yung
Allen Volchuk
Neil M. Goldenberg
Neil M. Goldenberg
Neil M. Goldenberg
Neil M. Goldenberg
Adria Giacca
Adria Giacca
Adria Giacca
Adria Giacca
author_facet S. M. Niazur Rahman
Justin Hou Ming Yung
Allen Volchuk
Neil M. Goldenberg
Neil M. Goldenberg
Neil M. Goldenberg
Neil M. Goldenberg
Adria Giacca
Adria Giacca
Adria Giacca
Adria Giacca
author_sort S. M. Niazur Rahman
collection DOAJ
description 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.
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publisher Frontiers Media S.A.
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series Frontiers in Immunology
spelling doaj-art-3353d385e8ec4083adefad7cd9d8269b2025-08-20T02:56:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.14998581499858Metabolic phenotypes in a Lyz2Cre recombinase mouse modelS. M. Niazur Rahman0Justin Hou Ming Yung1Allen Volchuk2Neil M. Goldenberg3Neil M. Goldenberg4Neil M. Goldenberg5Neil M. Goldenberg6Adria Giacca7Adria Giacca8Adria Giacca9Adria Giacca10Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaProgram in Cell Biology, The Hospital for Sick Children, Toronto, ON, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaProgram in Cell Biology, The Hospital for Sick Children, Toronto, ON, CanadaAnesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, CanadaDepartment of Anesthesiology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaDepartment of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaInstitute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaBanting and Best Diabetes Centre, University of Toronto, Toronto, ON, CanadaThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499858/fullCre-Lox P systemLyz2Cremacrophageglucose metabolisminsulin resistanceβ-cell dysfunction
spellingShingle S. M. Niazur Rahman
Justin Hou Ming Yung
Allen Volchuk
Neil M. Goldenberg
Neil M. Goldenberg
Neil M. Goldenberg
Neil M. Goldenberg
Adria Giacca
Adria Giacca
Adria Giacca
Adria Giacca
Metabolic phenotypes in a Lyz2Cre recombinase mouse model
Frontiers in Immunology
Cre-Lox P system
Lyz2Cre
macrophage
glucose metabolism
insulin resistance
β-cell dysfunction
title Metabolic phenotypes in a Lyz2Cre recombinase mouse model
title_full Metabolic phenotypes in a Lyz2Cre recombinase mouse model
title_fullStr Metabolic phenotypes in a Lyz2Cre recombinase mouse model
title_full_unstemmed Metabolic phenotypes in a Lyz2Cre recombinase mouse model
title_short Metabolic phenotypes in a Lyz2Cre recombinase mouse model
title_sort metabolic phenotypes in a lyz2cre recombinase mouse model
topic Cre-Lox P system
Lyz2Cre
macrophage
glucose metabolism
insulin resistance
β-cell dysfunction
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499858/full
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