Vertebrate Models to Investigate CCM Pathogenesis: The Zebrafish and Mouse Model

The use of vertebrate models allows researchers to investigate mechanisms of CCM pathogenesis in vivo, to investigate discrepancies between observations seen in the lab with in vitro experiments and how they translate into animal models; these in vivo models are more relevant in terms of CCM pathogenesis seen in humans than the in vitro counterparts. The use of CCM-deficient Zebrafish model offers advantages given their optical clarity during embryogenesis, short generation time, and high fecundity. When looking at the in vivo mouse model, gene conservation among CCM1, CCM2, and CCM3 is much higher among mammals (>92%), offering higher relevance in terms of similarities between what is seen in a mouse compared to human CCM pathogenesis. With both models, deficiencies in CCM1, CCM2, and CCM3 demonstrate perturbed cardiovascular development and underlying mechanisms of CCM pathogenesis at multiple stages seen in humans. The optimized methods described in this chapter allow researchers to benefit from both in vivo models, investigating impacts of deficiencies in CCM gene expression and its effect on angiogenesis and other signaling cascades, offering a much wider view of the molecular and cellular mechanisms in CCM progression.