In St8sia1 gene knockout mice (St8sia1-KO) lacking the GD3 synthase enzyme, a-series gangliosides accumulate, and b- and c-series gangliosides are deficient. Total concentration of gangiosides in the KO mice remains the same as in wild-type (WT) mice, while the ganglioside composition markedly changes. In the plasma membrane gangliosides are clustered in lipid rafts, same as connexins (Cx), that are transmembrane proteins critical for intercellular communication in many organs, and play a functional role in several regulatory mechanisms in kidney. Considering that altered ganglioside composition affects the distribution of proteins in lipid rafts of different cell membranes and in this way probably influences the distribution, transport, and function of different Cx isoforms, the aim of this study was to determine the effects of altered ganglioside composition on the expression of Cx37, Cx40, Cx43, Cx45, and Panx1 in different kidney regions of St8sia1-KO mice. Experiments were performed in twelve male 6-month-old mice: four wild-type (C57BL/6-type, WT) and eight St8sia1-KO mice. Mice kidney samples were processed for immunohistochemistry and analyzed. The expression of Cx37, Cx40, Cx43, Cx45 and Panx1 was examined by immunofluorescence microscopy (BX61, Olympus, Tokio, Japan), while quantitative evaluation of immunoreactivity was performed using ImageJ Software (National Institutes of Health, Bethesda, MD, SAD). To localize expression of connexins and Panx1 in different parts of the mice kidney, we performed double fluorescent staining with different tubular segment markers. The expression of connexins and Panx1 was determined in different regions of the kidney: cortex (CTX.), outer stripe of outer medulla (O.S.), inner stripe of outer medulla (IN.S.), and inner medulla (IN.MED.). Cx37, Cx40, Cx45, and Panx1 are significantly lower expressed in different parts of the kidneys of St8sia1-KO mice compared with WT. All of the above mentioned markers are decresased the most consistent in the O.S. in St8sia1-KO mice, so we can conclude that proximal tubules and thick ascending limbs are parts of the nephron most sensitive to changes in ganglioside composition. In the CTX. region reduced expression for Cx37, Cx45 and Panx1 was observed, while in the IN.S. region Cx37 and Panx1 were lower expressed. The results of the present study suggest that deficiency of GD3 synthase in St8sia1-KO mice leads to disturbance in renal Cx expression, which is probably related to alteration of ganglioside composition. The observed disruption of Cx expression in the kidney of St8sia1-KO mice gives important insight in changes on cellular level that can be seen in hyperglycemic conditions, and thus valuable informations for future studies. The disruption of ganglioside composition in the kidney of St8sia1-KO mice may be a good model for the alteration of ganglioside composition and properties of lipid rafts under diabetic conditions.