Mucopolysaccharidosis Type VI in Rats: Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation

Tetsuo Kunieda, CALOGERA M. SIMONARO, MIDORI YOSHIDA, HIROSHI IKADAI, GÖRAN LEVAN, ROBERT J. DESNICK, EDWARD H. SCHUCHMAN

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder caused by the deficiency of arylsulfatase B (ARSB) activity, occurs in humans, cats, and rats. To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding rat ARSB were isolated from a rat liver cDNA library. The nucleotide and deduced amino acid sequences of rat ARSB had ∼80 and 85% identity with the human ARSB sequences, respectively. The chromosomal location of the rat ARSB gene was determined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARSB gene was assigned to rat chromosome 2, where the locus for the MPS VI phenotype in rats has been localized by linkage analysis. To identify the mutation(s) within the ARSB gene causing MPS VI in rats, the ARSB sequence were amplified from affected animals and completely sequenced. Notably, a homoallelic one-base insertion at nucleotide 507 (507insC) was identified, resulting in a frame shift mutation and premature termination at codon 258. The presence of the insertion completely correlated with the occurrence of the MPS VI phenotype among 66 members of the MPR rat colony. Thus, we conclude that 507insC is the causative mutation in these animals and that the MPS VI rats are an authentic model of human MPS VI.

Original languageEnglish
Pages (from-to)582-587
Number of pages6
JournalGenomics
Volume29
Issue number3
DOIs
Publication statusPublished - Oct 1995
Externally publishedYes

Fingerprint

Mucopolysaccharidosis VI
N-Acetylgalactosamine-4-Sulfatase
Complementary DNA
Mutation
Genes
Nucleotides
Phenotype
Frameshift Mutation
Chromosomes, Human, Pair 2
Hybrid Cells
Nonsense Codon
Gene Library

ASJC Scopus subject areas

  • Genetics

Cite this

Kunieda, T., SIMONARO, CALOGERA. M., YOSHIDA, MIDORI., IKADAI, HIROSHI., LEVAN, GÖRAN., DESNICK, ROBERT. J., & SCHUCHMAN, EDWARD. H. (1995). Mucopolysaccharidosis Type VI in Rats: Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation. Genomics, 29(3), 582-587. https://doi.org/10.1006/geno.1995.9962

Mucopolysaccharidosis Type VI in Rats : Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation. / Kunieda, Tetsuo; SIMONARO, CALOGERA M.; YOSHIDA, MIDORI; IKADAI, HIROSHI; LEVAN, GÖRAN; DESNICK, ROBERT J.; SCHUCHMAN, EDWARD H.

In: Genomics, Vol. 29, No. 3, 10.1995, p. 582-587.

Research output: Contribution to journalArticle

Kunieda, T, SIMONARO, CALOGERAM, YOSHIDA, MIDORI, IKADAI, HIROSHI, LEVAN, GÖRAN, DESNICK, ROBERTJ & SCHUCHMAN, EDWARDH 1995, 'Mucopolysaccharidosis Type VI in Rats: Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation', Genomics, vol. 29, no. 3, pp. 582-587. https://doi.org/10.1006/geno.1995.9962
Kunieda, Tetsuo ; SIMONARO, CALOGERA M. ; YOSHIDA, MIDORI ; IKADAI, HIROSHI ; LEVAN, GÖRAN ; DESNICK, ROBERT J. ; SCHUCHMAN, EDWARD H. / Mucopolysaccharidosis Type VI in Rats : Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation. In: Genomics. 1995 ; Vol. 29, No. 3. pp. 582-587.
@article{65f20a31ceb64e2cad39dc47f47faaf1,
title = "Mucopolysaccharidosis Type VI in Rats: Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation",
abstract = "Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder caused by the deficiency of arylsulfatase B (ARSB) activity, occurs in humans, cats, and rats. To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding rat ARSB were isolated from a rat liver cDNA library. The nucleotide and deduced amino acid sequences of rat ARSB had ∼80 and 85{\%} identity with the human ARSB sequences, respectively. The chromosomal location of the rat ARSB gene was determined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARSB gene was assigned to rat chromosome 2, where the locus for the MPS VI phenotype in rats has been localized by linkage analysis. To identify the mutation(s) within the ARSB gene causing MPS VI in rats, the ARSB sequence were amplified from affected animals and completely sequenced. Notably, a homoallelic one-base insertion at nucleotide 507 (507insC) was identified, resulting in a frame shift mutation and premature termination at codon 258. The presence of the insertion completely correlated with the occurrence of the MPS VI phenotype among 66 members of the MPR rat colony. Thus, we conclude that 507insC is the causative mutation in these animals and that the MPS VI rats are an authentic model of human MPS VI.",
author = "Tetsuo Kunieda and SIMONARO, {CALOGERA M.} and MIDORI YOSHIDA and HIROSHI IKADAI and G{\"O}RAN LEVAN and DESNICK, {ROBERT J.} and SCHUCHMAN, {EDWARD H.}",
year = "1995",
month = "10",
doi = "10.1006/geno.1995.9962",
language = "English",
volume = "29",
pages = "582--587",
journal = "Genomics",
issn = "0888-7543",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Mucopolysaccharidosis Type VI in Rats

T2 - Isolation of cDNAs Encoding Arylsulfatase B, Chromosomal Localization of the Gene, and Identification of the Mutation

AU - Kunieda, Tetsuo

AU - SIMONARO, CALOGERA M.

AU - YOSHIDA, MIDORI

AU - IKADAI, HIROSHI

AU - LEVAN, GÖRAN

AU - DESNICK, ROBERT J.

AU - SCHUCHMAN, EDWARD H.

PY - 1995/10

Y1 - 1995/10

N2 - Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder caused by the deficiency of arylsulfatase B (ARSB) activity, occurs in humans, cats, and rats. To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding rat ARSB were isolated from a rat liver cDNA library. The nucleotide and deduced amino acid sequences of rat ARSB had ∼80 and 85% identity with the human ARSB sequences, respectively. The chromosomal location of the rat ARSB gene was determined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARSB gene was assigned to rat chromosome 2, where the locus for the MPS VI phenotype in rats has been localized by linkage analysis. To identify the mutation(s) within the ARSB gene causing MPS VI in rats, the ARSB sequence were amplified from affected animals and completely sequenced. Notably, a homoallelic one-base insertion at nucleotide 507 (507insC) was identified, resulting in a frame shift mutation and premature termination at codon 258. The presence of the insertion completely correlated with the occurrence of the MPS VI phenotype among 66 members of the MPR rat colony. Thus, we conclude that 507insC is the causative mutation in these animals and that the MPS VI rats are an authentic model of human MPS VI.

AB - Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder caused by the deficiency of arylsulfatase B (ARSB) activity, occurs in humans, cats, and rats. To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding rat ARSB were isolated from a rat liver cDNA library. The nucleotide and deduced amino acid sequences of rat ARSB had ∼80 and 85% identity with the human ARSB sequences, respectively. The chromosomal location of the rat ARSB gene was determined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARSB gene was assigned to rat chromosome 2, where the locus for the MPS VI phenotype in rats has been localized by linkage analysis. To identify the mutation(s) within the ARSB gene causing MPS VI in rats, the ARSB sequence were amplified from affected animals and completely sequenced. Notably, a homoallelic one-base insertion at nucleotide 507 (507insC) was identified, resulting in a frame shift mutation and premature termination at codon 258. The presence of the insertion completely correlated with the occurrence of the MPS VI phenotype among 66 members of the MPR rat colony. Thus, we conclude that 507insC is the causative mutation in these animals and that the MPS VI rats are an authentic model of human MPS VI.

UR - http://www.scopus.com/inward/record.url?scp=0028844034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028844034&partnerID=8YFLogxK

U2 - 10.1006/geno.1995.9962

DO - 10.1006/geno.1995.9962

M3 - Article

C2 - 8575749

AN - SCOPUS:0028844034

VL - 29

SP - 582

EP - 587

JO - Genomics

JF - Genomics

SN - 0888-7543

IS - 3

ER -