Key result
Strain 129 background drives a ~17-fold increase in post-injury neointima formation vs DBA mice.
Why the study?
The influence of the genetic background of mice on vascular injury response has not yet received sufficient consideration.
Effect estimate: 17-fold increase
Absolute Event Rate: 9180% vs 540%
p-value: p=< 0.001
The genetic background of mice significantly influences the vascular injury response, highlighting the importance of strain selection in restenosis models.
Strain selection may confound murine restenosis models; leaves open optimal background for translational studies.
Mouse models are employed to unravel the pathophysiology of vascular restenosis. Although much effort has been spent on how to apply an adequate arterial injury, the influence of the genetic background of mice has not yet received sufficient consideration. The study presented herein was designed to demonstrate the influence of the mouse strain on vascular injury response. Mice of a defined background (50% 129 strain and 50% DBA strain) were backcrossed into either the 129 strain or the DBA strain. Male offspring were subjected to a femoral artery injury model by applying an electric current. Morphometric analysis revealed that backcrossing into the 129 strain resulted in a significant (P < 0.001) 17-fold increase in neointima formation (n = 17 mice) compared with backcrossing into the DBA strain (n = 19). The values of neointima area were 9.18 x 10(3) +/- 2.13 x 10(3) and 0.54 x 10(3) +/- 0.39 x 10(3) microm2, respectively. In conjunction, the vessel wall area was enhanced by 1.8-fold (P < 0.001). In contrast, no significant differences were found for the areas of the lumen and the tunica media. Similarly, a significant increase in neointima formation was also found for mice of pure 129 strain compared with pure DBA strain. The results underline the importance of the genetic background for studies on vascular injury response. Furthermore, because the mouse genome of the various strains is well defined, serial testing of the genetic background of mice will provide candidate genes and/or genetic modifiers controlling vascular injury response.
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Sindermann et al. (2005) studied Vascular restenosis (n=36). Backcrossing into the 129 strain vs. Backcrossing into the DBA strain was evaluated on Neointima formation area (microm2) (17-fold increase, p=< 0.001). Backcrossing mice into the 129 strain resulted in a significant 17-fold increase in neointima formation following femoral artery injury compared with backcrossing into the DBA strain (P < 0.001).
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