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Tissue-specific Cre driver mice to study vascular diseases
1Medical Research Center, Chongqing General Hospital, Chongqing 401147, China; Chongqing Academy of Medical Sciences, Chongqing 401147, China.
Abstract:
Vascular diseases, including atherosclerosis and abdominal aneurysms, are the primary cause of mortality and morbidity among the elderly worldwide. The life quality of patients is significantly compromised due to inadequate therapeutic approaches and limited drug targets. To expand our comprehension of vascular diseases, gene knockout (KO) mice, especially conditional knockout (cKO) mice, are widely used for investigating gene function and mechanisms of action. The Cre-loxP system is the most common method for generating cKO mice. Numerous Cre driver mice have been established to study the main cell types that compose blood vessels, including endothelial cells, smooth muscle cells, and fibroblasts. Here, we first discuss the characteristics of each layer of the arterial wall. Next, we provide an overview of the representative Cre driver mice utilized for each of the major cell types in the vessel wall and their most recent applications in vascular biology. We then go over Cre toxicity and discuss the practical methods for minimizing Cre interference in experimental outcomes. Finally, we look into the future of tissue-specific Cre drivers by introducing the revolutionary single-cell RNA sequencing and dual recombinase system.
Insights
Gene knockout mice, particularly conditional knockout (cKO) models using the Cre-loxP system, are crucial for understanding vascular diseases like atherosclerosis. This review highlights Cre driver mice for vessel cell types and discusses minimizing Cre toxicity for accurate research outcomes.
Area of Science:
- Vascular biology and disease research.
- Genetics and molecular biology.
- Animal models for disease mechanisms.
Background:
- Vascular diseases are a leading cause of death in the elderly, with limited treatment options.
- Gene knockout (KO) and conditional knockout (cKO) mice are vital tools for studying gene function in vascular diseases.
- The Cre-loxP system is the primary method for generating cKO mice.
Purpose of the Study:
- To review Cre driver mouse lines for studying major vascular cell types (endothelial cells, smooth muscle cells, fibroblasts).
- To discuss the characteristics of arterial wall layers.
- To explore strategies for mitigating Cre toxicity in experimental models.
Main Methods:
- Review of existing literature on Cre driver mice and their applications in vascular biology.
- Discussion of the Cre-loxP system and its use in generating cKO mice.
- Analysis of Cre toxicity and methods to minimize its interference.
Main Results:
- Overview of established Cre driver mouse lines for specific vascular cell types.
- Summary of recent applications of these models in vascular research.
- Identification of Cre toxicity as a potential confounding factor and proposed solutions.
Conclusions:
- Cre driver mice are indispensable for dissecting gene function in vascular disease.
- Careful consideration of Cre toxicity is necessary for reliable experimental results.
- Future directions include advanced systems like single-cell RNA sequencing and dual recombinase systems for enhanced tissue-specific gene manipulation.
