title: Porcine N-acetylgalactosamine 6-sulfatase (GALNS) cDNA sequence and expression in developing teeth.
abstract: Mucopolysaccharidosis type IVA (Morquio A syndrome, MPS IVA) is a rare, autosomal recessive disorder with a prevalence of 1 in 170,000 live births. It is caused by a deficiency of N-acetylgalactosamine 6-sulfatase (GALNS), a lysosomal hydrolase encoded by a gene on human chromosome 16q24.3. Mucopolysaccharidosis type IVA is the only known MPS that is associated with structural defects in dental enamel. GALNS cleaves the sulfate group from N-acetylgalactosamine 6-sulfate and galactose 6-sulfate, which are specifically found in keratan sulfate and chondroitin 6-sulfate. A pathologic absence of GALNS activity results in the accumulation of these glycosaminoaglycans in the urine and in the lysosomes of tissues that turn them over. There is currently no animal model for MPS IVA. To learn more about how a GALNS deficit could lead to enamel defects, we have cloned and characterized a full-length pig GALNS cDNA. GALNS mRNA was localized in developing teeth by in situ hybridization, Northern blot, and reverse-transcription polymerase chain reaction analyses, while GALNS substrates were localized using immunohistochemistry. We report that secretory ameloblasts were positive for GALNS mRNA, as well as for keratan sulfate and chondroitin 6-sulfate. We conclude that enamel defects associated with the loss of GALNS activity in persons with MPS IVA are likely to result from the pathological accumulation of keratan sulfate and chondroitin 6-sulfate in the lysosomes of secretory stage ameloblasts.
authors.affiliation: University of Texas School of Dentistry, Health Science Center at San Antonio, Department of Pediatric Dentistry, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamakoshi
authors.forename: Jan C C
authors.initials: JC
authors.lastname: Hu
authors.forename: Shengxi
authors.initials: S
authors.lastname: Liu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Sun
authors.forename: Chuhua
authors.initials: C
authors.lastname: Zhang
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Oida
authors.forename: Makato
authors.initials: M
authors.lastname: Fukae
authors.forename: James P
authors.initials: JP
authors.lastname: Simmer
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002809:Chondroitin Sulfates / Q000378:metabolism; D002811:Chondroitinsulfatases / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics*; D015870:Gene Expression; D007150:Immunohistochemistry; D007632:Keratan Sulfate / Q000378:metabolism; D008969:Molecular Sequence Data; D009805:Odontogenesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine / Q000235:genetics* / Q000254:growth & development*; D014070:Tooth / Q000502:physiology
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D002809:Chondroitin Sulfates; D007632:Keratan Sulfate; D002811:Chondroitinsulfatases