The mouse N-acetylgalactosamine-6-sulfate sulfatase (Galns) gene: cDNA isolation, genomic characterization, chromosomal assignment and analysis of the 5'-flanking region

Adriana Maria Montaño, Atsushi Yamagishi, Shunji Tomatsu, Seiji Fukuda, Neal G. Copeland, Kenji E. Orii, Koji Isogai, Naoto Yamada, Zen Ichiro Kato, Nancy A. Jenkins, Debra J. Gilbert, Kazuko Sukegawa, Tadao Orii, Naomi Kondo

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Deficiency of lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) leads to mucopolysaccharidosis IV A (MPS IV A), for which there is no definitive treatment so far. Although a number of mutations of the GALNS gene of MPS IV A patients have been described, pathogenesis of the disorder still remains elusive. In order to facilitate in vivo studies using model animals for MPS IV A, we isolated and performed molecular characterization of the mouse homolog of human GALNS. The 2.3-kb cDNA contains a 1560-bp open reading frame encoding 520 amino acid residues. The coding region has 84% similarity to the human GALNS cDNA at amino acid level. The mouse Galns gene was mapped by interspecific backcross analysis to the distal region of chromosome 8 where it co-segregates with Aprt. Northern blot analysis showed a wide expression of a single-copy gene, being higher especially in liver and kidney. The Galns gene was isolated from S129vJ genomic library and its genomic organization was characterized. The mouse Galns gene was about 50-kb long and organized into 14 exons and 13 introns. All intron-exon splice junctions conformed to the GT/AG consensus sequence except exon 8/intron 8 junction. Primer extension shows multiple transcription initiation sites between -44 and -75 although major transcription initiation site was observed at -90 bp from the ATG codon. The 5'-flanking region lacks canonical TATA and CAAT box sequences, but is G+C rich with 10 GC boxes (potential Sp1 binding sites), characteristic of a housekeeping gene promoter. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)323-334
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1500
Issue number3
DOIs
StatePublished - Mar 17 2000

Keywords

  • Galns gene
  • Lysosomal storage disease
  • Morquio disease
  • Mouse
  • Mucopolysaccharidosis IV A

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

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