Title

Differences between mouse strains in disease distribution, geometry, and hemodynamics

Mice deficient in the apo-E gene (apo-E knockout mice) develop atherosclerotic arterial disease similar to that in humans. The disease in the mouse aortic arch is distributed differently in the C57BL/6 (B6) and 129/SvEv (129) strains (Fig. 1). Since vascular geometry may play an important role in the non-uniform development of atherosclerosis by modulating hemodynamic stresses at the vessel wall, we are examining the differences in aortic arch geometry and wall shear stress distribution between the two strains. The 3-D geometry of fourteen mouse aortic arches, seven from each strain, was characterized from vascular casts using optical stereo-microscopic imaging (Fig. 2). Three sets of geometric features were calculated from each cast, defining the shape of the arch, vessel diameters, and branch locations. All of these geometric features differed significantly between the two mouse strains (Fig. 3). Initial computational fluid dynamic simulations indicate that the 129 mouse strain is exposed to much lower shear stresses at the inner wall of the aortic arch than the B6 strain, which correlates to the greater involvement of this region in the former mice. These results provide new evidence for the existence of “geometric risk factors” for cardiovascular disease.

Fig. 1. Typical different disease patterns in B6 and 129 apoE knockout mice.

Fig. 2. The aortic cast of a B6 mouse and its reconstructed 3-D axis using optical stereo-microscopic imaging

Fig. 3. average shapes of the 2D projections of B6 and 129 mice (* – branch locations, first O – point of symmetry of the arch); Right: average vessel diameters of the two strains (Blue – B6; Red – 129; Solid line – in-plane diameter; dotted line – out-of-plane diameter; dots – branch locations).

Fig. 4. The 129 strain (red curve in the left-hand panel) experiences lower shear stress along the inner wall of the aortic arch than the B6 strain (blue curve). The abscissa of the panel to the left is indicated by the blue lines along the inner curvature of the arch in the panels on the right.

Back to Research