Mouse models of vascular development and disease

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalCurrent opinion in hematology
Volume28
Issue number3
DOIs
StatePublished - May 1 2021

ASJC Scopus subject areas

  • Hematology

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