Background: Waardenburg syndrome is a common syndromic hereditary deafness disease caused by stria vascularis dysfunction. However, the genetic pathway affecting stria vascularis development is still not clear. In this paper, the transcript profile of stria vascularis of Waardenburg syndrome was studied using Mitf-M mutant pigs and mice models. GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation. Results: There were over than one hundred genes mainly found in tyrosine metabolism, melanin formation and ion transportations showed significant changes in both models. In addition, there were some spiced specific gene changes in the stria vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19 and Cdh24 genes, were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the stria vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1 and Col11a2 genes were higher and the expression of Col8a2, Cd34 and Ncam genes were lower in the porcine model compared to mouse model. In both models, Trpm1, Kcnj13, and Slc45a2 genes were both affected by the Mitf-M mutation. In the pig models, the expression of Kcnn1, Clcn2 and Trpm4 genes were higher than the mouse model; whereas the expression of Trpm7, Kcnq1 and Kcnj8 genes were higher in the mouse models than the pig models. However, there was no significant difference in the morphology of the stria vascularis between these two models. Conclusions: Our data suggests that there is a significant difference on the gene expression and function between these two models.