Human gene encoding human chondroitin 6-sulfotransferase

Details Human gene encoding human chondroitin 6-sulfotransferase Human gene encoding human chondroitin 6-sulfotransferase

1998-01-29

2002-06-04

Prouty, Rebecca E. (Department: 1652)

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Bacteria or actinomycetales; media therefor

C536S023200, C435S193000, C435S325000, C435S300100

Reexamination Certificate

active

06399358

ABSTRACT:

BACKGROUND OF THE INVENTION
Chondroitin sulfate is an important component of the extracellular matrix of animals. Chondroitin 6-sulfate (C6S), the form that is sulfated at position 6 of its N-acetylgalactosamine residues, has been implicated in several key roles in human biology, including development (Toledo et al.
Am. J. Med. Gen
. 1978, 2:385-395; Mourao et al,
Biochem. Biophys. Res. Commun
. 1981, 98:388-396; Habuchi et al.
J. Biol. Chem
. 1986, 261:1031-1040), cancer (Adany et al.
J. Biol. Chem
. 1990, 265:11389-11396), and atherosclerosis (Williams, K. J. and Tabas, I.
Arterioscl. Thromb. Vasc. Biol
. 1995, 15:551-561). The abundance of C6S is under genetic (Edwards, I. J. and Wagner, W. D.
J. Biol. Chem
. 1988, 263:9612-9620) and stimulatory (Schonherr et al.
J. Biol. Chem
. 1991, 266:17640-17647) control. Fukata et al. recently cloned the chick cDNA encoding C6ST, the essential enzyme in C6S synthesis (
J. Biol. Chem
. 1995, 270:18575-18580).
A human genomic DNA encoding C6ST has now been cloned and sequenced.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a gene encoding human chondroitin 6-sulfotransferase.
Another object of the present invention is to provide vectors comprising genes encoding human chondroitin 6-sulfotransferase and host cells containing these vectors.
Yet another object of the present invention is to provide polypeptides encoded by human chondroitin 6-sulfotransferase.
Yet another object of the present invention is to provide nonhuman transgenic animals capable of encoding a gene of the present invention.
Yet another object of the present invention is to provide methods of identifying activators and inhibitors of expression, activities and biologic effects of human chondroitin 6-sulfotransferase.
Still another object of the present invention is to provide methods of identifying mutations in the genes encoding human chondroitin 6-sulfotransferase.


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M. Fukuta et al., “Molecular Cloning and Characterization of Human Keratan Sulfate Gal-6-Sulfotransferase”, J. Biol. Chem. 272(51):32321-32328, Dec. 1997.*
H. Inoue et al. “Glycosaminoglycan sulfotransferases in human and animal sera”, J.Biol. Chem. 261(10) 4460-9, Apr. 1986.*
GenBank Accession No. H16077, Jul. 1995.*
Adany et al., “Altered Expression of Chondroitin Sulfate Proteoglycan in the Stroma of Human Colon Carcinoma”,J. Biol. Chem.1990, 265:11389-11396.
Edwards, I.J. and Wagner, W.D., “Distinct Synthetic and Structural Characteristics of Proteoglycans Produced by Cultured Artery Smooth Muscle Cells of Atherosclerosis-susceptible Pigeons”,J. Biol. Chem.1988, 263:9612-9620.
Esko et al., “Sulfate Transport-deficient Mutants of Chinese Hamster Ovary Cells”,J. Biol. Chem.1986, 261, 15725-15733.
Fukata et al., “Molecular Cloning and Expression of Chick Chondrocyte Chondroitin 6-Sulfotransferase”,J. Biol. Chem.1995, 270:18575-18580.
Fuki et al., “The Syndecan Family of Proteoglycans”,J. Clin. Invest.1997, 100, 1611-1622.
Habuchi et al., “Changes in Proteoglycan Composition during Development of Rat Skin”,J. Biol. Chem.1986, 261:1031-1040.
Lennon et al., “The I.M.A.G.W. Consortium: An Integrated Molecular Analysis of Genomes and Their Expression”,Genomics1996, 33:151-152.
Mourao et al., “Spondyloepiphyseal Dysplasia, Chrondroitin Sulfate Type: A Possible Defect of Paps—Chrondroitin Sulfate Sulfotransferase in Humans”,Biochem. Biophys. Res. Commun.1981, 98:388-396.
Schonherr et al., “Effects of Platelet-derived Growth Factor and Transforming Growth Factor-&bgr;1 on the Synthesis of a Large Versican-like Chrondroitin Sulfate Proteoglycan by Arterial Smooth Muscle Cells”,J. Biol. Chem.1991, 266:17640-17647.
Toledo et al., “Recessively Inherited, Late Onset Spondylar Dysplasia and Peripheral corneal Opacity With Anomalies in Urinary Mucopolysaccharides: A Possible Error of Chrondroitin-6-Sulfate Synthesis”,Am. J. Med. Gen.1978, 2:385-395.
Wasserman et al., “Use of thin-layer chromatography in the separation of disaccharides resulting from digestion of chondroitin sulphates with chondroitinases”,J. Chromatogr.1977, 136, 342-347.
Williams, K.J. and Tabas, I., “The Response-to-Retention Hypothesis of Early Athergenesis”,Arterioscl. Thromb. Vasc. Biol.1995, 15:551-561.

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