Functional Analysis of the Chondroitin 6-Sulfotransferase Gene in Relation to Lymphocyte Subpopulations, Brain Development, and Oversulfated Chondroitin Sulfates

Abstract

Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. To obtain direct evidence regarding the function of C6ST and its product, chondroitin 6-sulfate, in vivo, we isolated the mouse C6ST gene (C6st) and generated mice deficient in this gene (C6st ؊/؊ ) by embryonic stem cell technology. C6st؊/؊ mice were born at approximately the expected frequency and were viable through adulthood. In the spleen of C6st ؊/؊ mice, the level of chondroitin 6-sulfate became almost undetectable. Analyses of these knockout mice provided insights into the biosynthesis of oversulfated chondroitin sulfates in mice; chondroitin sulfate D in the brain of null mice and the cartilage and telencephalon of null embryos disappeared, whereas the chondroitin sulfate E level in the spleen and brain of the null mice was unchanged. Despite the disappearance of chondroitin sulfate D structure, brain development was normal in the C6st ؊/؊ mice. Further analysis revealed that the number of CD62L ؉ CD44 low T lymphocytes corresponding to naive T lymphocytes in the spleen of 5-6-week-old C6st ؊/؊ mice was significantly decreased, whereas those in other secondary lymphoid organs were unchanged. This finding suggested that chondroitin 6-sulfate plays a role in the maintenance of naive T lymphocytes in the spleen of young mice.

Isolation and characterization of heparan sulfate from various murine tissues

“…Study on knock-out mice provided insights of biosynthesis of oversulfated PGs in mice brain [13,40]. Our studies on bovine brain HS showed that it was more highly sulfated than standard bovine kidney HS [41].…”

Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement

“…In the mouse, C6ST-1 was found in spleen and lung but also in eye, stomach, ovary, kidney, and, dependent on the developmental stage, in brain (17). Recently, the function of C6ST-1 has been further elucidated by inactivating CHST3 in the mouse (18). CHST3 Ϫ/Ϫ mice were born at the expected frequency and were viable through adulthood.…”

N-Acetylglucosamine 6-O-Sulfotransferase-1 Regulates Expression of L-Selectin Ligands and Lymphocyte Homing

“…Generation of Targeted ES Cells and Mice-Aliquots of 17 g of ScaIlinearized targeting vector DNA were electroporated into 1 ϫ 10 7 D3 ES cells (33), and homologously recombined cells were selected as described previously (34). The production of chimeric mice, which are derived from the targeted ES clones, was carried out as described previously (34).…”

“…The production of chimeric mice, which are derived from the targeted ES clones, was carried out as described previously (34). Chimeric male mice were bred with C57BL/6J mice.…”