Murine Models of Vascular Disease

Transgenic mice provide a powerful tool to study the molecular determinants of the vascular response to injury. Traditionally, antibodies or receptor agonists and antagonists were used to dissect out the multitude of molecules involved in the cascades leading to pathologic remodeling. Transgenic mice, on the other hand, avoid many of the difficulties associated with antibodies such as incomplete or nonspecific antibody binding, and the efficacy/side effect issues with receptor agonists and antagonists. Additionally, the use of transgenic mice allows study of the complex biologic events of gene function in an in vivo, rather than in vitro model. Murine genetics and the ability to manipulate mouse genes are quite advanced compared to other species, and mice are relatively easy to handle and inexpensive to house.

Mechanical arterial wall injury models using animals such as rats and rabbits have generated considerable new knowledge in vascular biology. However, arterial wall investigations in mice have been hampered by their small size and lack of appropriate injury models.

 


Murine common carotid artery

Neointimal hyperplasia in a mouse carotid

Previous murine models have included inbreeding and dietary interventions, and transgenic mice with altered lipid metabolism, such as Apo E deficient mice. Such biologic perturbations have obvious experimental limitations. Common carotid artery endothelial denuding wire injury models can be technically demanding since they require opening the tiny mouse external carotid artery.

Our laboratory holds a long interest in finding better mouse models of vascular disease. Combined with recent advances in murine genetics and gene therapy, these efforts may one day provide powerful tools for the molecular dissection of vascular biological mechanisms in health and disease.


Transgenic mouse

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