Physiological roles of N-acetylglucosaminyltransferase V (GnT-V) in mice
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Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), a glycosyltransferase encoded by the Mgat5gene that catalyzes the formation of β1,6GlcNAc (N-acetylglucosamine)branches on N-glycans, is thought to be associated with cancer growth and metastasis. Overexpression of GnT-V in cancer cells enhances the signaling of growth factors such as epidermal growth factor by increasing galectin-3 binding to polylactosamine structures on receptor N-glycans. In contrast, GnT-V deficient mice are born healthy and lack β1,6GlcNAc branches on N-glycans, but develop immunological disorders due to T-cell dysfunction at 12-20months of age. We have developed Mgat5 transgenic (Tg)mice (GnT-V Tg mice) using a β-actin promoter and found characteristic phenotypes in skin, liver, and T cells in the mice. Although the GnT-V Tg mice do not develop spontaneous cancers in any organs, there are differences in the response to external stimuli between wild-type and GnT-V Tg mice. These changes are similar to those seen in cancer progression but are unexpected in some aspects. In this review, we summarize what is known about GnT-V functions in skin and liver cells as a means to understand the physiological roles of GnT-V in mice. [BMB Reports 2012; 45(10): 554-559]
Abstract
Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), a glycosyltransferase encoded by the Mgat5gene that catalyzes the formation of β1,6GlcNAc (N-acetylglucosamine)branches on N-glycans, is thought to be associated with cancer growth and metastasis. Overexpression of GnT-V in cancer cells enhances the signaling of growth factors such as epidermal growth factor by increasing galectin-3 binding to polylactosamine structures on receptor N-glycans. In contrast, GnT-V deficient mice are born healthy and lack β1,6GlcNAc branches on N-glycans, but develop immunological disorders due to T-cell dysfunction at 12-20months of age. We have developed Mgat5 transgenic (Tg)mice (GnT-V Tg mice) using a β-actin promoter and found characteristic phenotypes in skin, liver, and T cells in the mice. Although the GnT-V Tg mice do not develop spontaneous cancers in any organs, there are differences in the response to external stimuli between wild-type and GnT-V Tg mice. These changes are similar to those seen in cancer progression but are unexpected in some aspects. In this review, we summarize what is known about GnT-V functions in skin and liver cells as a means to understand the physiological roles of GnT-V in mice. [BMB Reports 2012; 45(10): 554-559]
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