Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates.
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.
Uchimura
Kenji
K
Department of Biochemistry, the Laboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya 466-8550, Japan.
Kadomatsu
Kenji
K
Nishimura
Hitoshi
H
Muramatsu
Hisako
H
Nakamura
Eishin
E
Kurosawa
Nobuyuki
N
Habuchi
Osami
O
El-Fasakhany
Fathy M
FM
Yoshikai
Yasunobu
Y
Muramatsu
Takashi
T
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D001923:Brain Chemistry; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000737:chemistry / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018390:Gene Targeting; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013154:Spleen / Q000737:chemistry / Q000166:cytology; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D000097811:Carbohydrate Sulfotransferases
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases