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Updated: Nov 11, 2025
In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
Published on: May 11, 2021
Mouse models of vascular development and disease
1Department of Molecular Biology, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Purpose Of Review:
The use of genetic models has facilitated the study of the origins and mechanisms of vascular disease. Mouse models have been developed to specifically target endothelial cell populations, with the goal of pinpointing when and where causative mutations wreck their devastating effects. Together, these approaches have propelled the development of therapies by providing an in-vivo platform to evaluate diagnoses and treatment options. This review summarizes the most widely used mouse models that have facilitated the study of vascular disease, with a focus on mouse models of vascular malformations and the road ahead.
Recent Findings:
Over the past 3 decades, the vascular biology scientific community has been steadily generating a powerful toolkit of useful mouse lines that can be used to tightly regulate gene ablation, or to express transgenic genes, in the murine endothelium. Some of these models inducibly (constitutively) alter gene expression across all endothelial cells, or within distinct subsets, by expressing either Cre recombinase (or inducible versions such as CreERT), or the tetracycline controlled transactivator protein tTA (or rtTA). This now relatively standard technology has been used to gain cutting edge insights into vascular disorders, by allowing in-vivo modeling of key molecular pathways identified as dysregulated across the vast spectrum of vascular anomalies, malformations and dysplasias. However, as sequencing of human patient samples expands, the number of interesting candidate molecular culprits keeps increasing. Consequently, there is now a pressing need to create new genetic mouse models to test hypotheses and to query mechanisms underlying vascular disease.
Summary:
The current review assesses the collection of mouse driver lines that have been instrumental is identifying genes required for blood vessel formation, remodeling, maintenance/quiescence and disease. In addition, the usefulness of these driver lines is underscored here by cataloguing mouse lines developed to experimentally assess the role of key candidate genes in vascular malformations. Despite this solid and steady progress, numerous new candidate vascular malformation genes have recently been identified for which no mouse model yet exists.
Insights
Genetic mouse models are crucial for understanding vascular disease mechanisms and developing new therapies. New models are needed to study newly identified genes in vascular malformations.
Area of Science:
- Vascular biology
- Genetics
- Disease modeling
Background:
- Genetic models, particularly mouse models, are vital for studying vascular disease origins and mechanisms.
- Targeting endothelial cells in mice helps pinpoint the effects of causative mutations.
- These models provide an in-vivo platform for evaluating diagnoses and treatments.
Purpose of the Study:
- To summarize widely used mouse models for studying vascular disease.
- To focus on mouse models of vascular malformations and future directions.
- To assess the collection of mouse driver lines instrumental in identifying genes for blood vessel formation and disease.
Main Methods:
- Utilizing mouse lines to regulate gene ablation or transgenic gene expression in murine endothelium.
- Employing Cre recombinase or tetracycline-controlled transactivator protein systems for inducible or constitutive gene expression alteration.
- Cataloguing existing mouse lines to assess candidate genes in vascular malformations.
Main Results:
- Over three decades, a robust toolkit of mouse lines has been developed for vascular biology research.
- These models allow for in-vivo modeling of molecular pathways in vascular anomalies, malformations, and dysplasias.
- Progress has been made in identifying genes involved in blood vessel formation, remodeling, and maintenance.
Conclusions:
- Genetic mouse models have significantly advanced the study of vascular disease.
- Existing models are instrumental in understanding vascular malformations.
- There is an ongoing need for new genetic mouse models to investigate newly identified candidate genes in vascular disease.
