The core polypeptide of cystic fibrosis tracheal mucin contains a tandem repeat structure. Evidence for a common mucin in airway and gastrointestinal tissue.

Gérard, Craig; Eddy, Roger L.; Shows, Thomas B.

doi:10.1172/jci114925

Cited by 63 publications

(25 citation statements)

References 23 publications

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“…Discussion MUC-2 polymorphisms. All four of the currently known human mucin genes have been found to be polymorphic (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The MUC-1 gene has been the most thoroughly examined in this respect.…”

Section: Resultsmentioning

confidence: 99%

“…Four human mucins have been described and at least partially characterized (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). All of these genes have been found Our laboratory has cloned partial cDNAs that are derived from two different human intestinal mucin genes, MUC-2 and MUC-3 (9,13).…”

Section: Introductionmentioning

confidence: 99%

“…The MUC-2 cDNAs were the first isolated and are the better characterized ofthe two. This gene is expressed in colon, small intestine, colonic tumors, bronchus, cervix, gall bladder, and possibly other tissues, suggesting that the MUC-2 gene product is physiologically important in many organ systems (9)(10)(11)(12). In addition, mucin abnormalities have been described in a number of gastrointestinal diseases including cystic fibrosis, ulcerative colitis, and colon cancer (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

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MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

Toribara¹,

Gum²,

Culhane³

et al. 1991

J. Clin. Invest.

172

106

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MUC-2, the first described intestinal mucin gene, has become important as a prototype for secreted mucins in several organ systems. However, little is known about its protein backbone structure and hence its role in diseases such as colon cancer, ulcerative colitis, and cystic fibrosis, which are known to have mucin abnormalities. Studies in this manuscript show that MUC-2 contains two distinct regions with a high degree of internal homology, but the two regions bear no significant homology to each other. Region 1 consists mostly of48-bp repeats which are interrupted in places by 21-24-bp segments. Several of these interrupting sequences show similarity to each other, creating larger composite repeat units. Region 1 has no length polymorphisms. Region 2 is composed of69-bp tandem repeats arranged in an uninterrupted array of up to 115 individual units. Southern analysis of genomic DNA samples using TaqI and HinfI reveals both length and sequence polymorphisms which occur within region 2. The sequence polymorphisms have different ethnic distributions, while the length polymorphisms are due to variable numbers of tandem repeats. (J. Clin. Invest.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

Toribara¹,

Gum²,

Culhane³

et al. 1991

J. Clin. Invest.

172

106

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“…*Despite the success of MUC1 VNTR-reactive MAbs, only a few MAbs reacting with other VNTR have been reported Price et al, 1991), and the use of these MAbs for diagnosis and therapy has not been investigated. The MUC2 mucin is of particular interest since this is a major component of mucus produced by patients with colon and lung cancer, as well as those with cystic fibrosis (Gum et al, 1989;Gerard et al, 1990;Jany et al, 1991). Subsequently, by immunising with native colon cancer mucin and a KLH-synthetic peptide conjugate containing the 23 amino acid MUC2 VNTR sequence, we have produced anti-MUC2 VNTR MAbs which react with the intact mucin.…”

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confidence: 99%

Monoclonal antibodies reacting with the MUC2 mucin core protein

Pl¹,

McGuckin²,

Birrell³

et al. 1993

Br J Cancer

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Summary This study sought to produce monoclonal antibodies (MAbs) which reacted with the MUC2 core protein. Two MAbs [3A2 (IgGl) and 4F1 (IgM)] were produced by immunising female BALB/c mice with gel-formed mucin from the LS174T colon cancer cell line followed by a KLH conjugate of a 29 amino acid synthetic peptide whose sequence was derived from the variable number of tandem repeats (VNTR) region of a MUC2 cDNA clone.The MAbs reacted with synthetic MUC2 VNTR peptides but not synthetic MUCI or MUC3 VNTR peptides, and showed specific reactivity in Western blotting with a high molecular weight protein produced by the LS174T colon carcinoma cell line. The use of shorter peptides indicated that the minimum peptide epitopes for these MAbs were different. Mab 3A2 reacted with amino acids 5-19 of the MUC2 VNTR by inhibition ELISA but not by direct ELISA, while 4FI reacted with this peptide in both assays. Furthermore, 4FI reacted in direct ELISA when a larger (29 amino acid) MUC2-derived peptide was coated onto the assay plate by incubating in carbonate buffer or by drying the peptide onto the assay plate, while 3A2 only reacted when this peptide was coated in carbonate buffer. The different specificity of the MAbs was also illustrated by the reactivity of 4F1 but not 3A2 with partially deglycosylated cystic fibrosis mucin.Immunohistochemical analysis with these MAbs revealed a strong reactivity with lung, gastric and colon tumours relative to normal tissue, with some breast and ovarian tumours also reacting. Both MAbs stained some normal goblet cells in the perinuclear region but not the mucin droplet or secreted mucin, indicating a reaction with immature (poorly glycosylated) mucin in the endoplasmic reticulum and/or golgi, but not with mature (fully glycosylated) mucin. In contrast, tumours showed strong diffuse cytoplasmic staining. 4F1 also showed weak apical cytoplasmic staining in some goblet cells and stained some tumours which showed no reactivity with 3A2.These antibodies should prove useful in the study of MUC2 structure and function, and in the diagnosis of some tumours.

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“…So far, nine families of cDNAs encoding human mucins have been cloned from breast tumour cells (MUCI) [2,3,4] jejunum mucosa as well as tracheobronchial mucosa (MUC2) [5,6,7], jejunum mucosa (MUC3) [8], tracheobronchial mucosa (MUC4, 5A, 5B, 5C) [9,10], stomach (MUC6) [11] and submandibular gland (MUC7) [12].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes?

Duperat

Audie

Debailleul

et al. 1995

Biochemical Journal

193

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To date five human mucin cDNAs (MUC2, 5A, 5B, 5C and 6) mapped to 11p15.3-15.5, so it appears that this chromosome region might contain several distinct gene loci for mucins. Three of these cDNAs, MUC5A, B and C, were cloned in our laboratory and previously published. A common number, 5, was recommended by the Human Gene Mapping Nomenclature Committee to designate them because of their common provenance from human tracheobronchial mucosa. In order to define whether they are products of the same gene locus or distinct loci, we describe in this paper physical mapping of these cDNAs using the strategy of analysis of CpG islands by pulse-field gel electrophoresis. The data suggest that MUC5A and MUC5C are part of the same gene (called MUC5AC) which is distinct from MUC5B. In the second part of this work, complete sequences of the inserts corresponding to previously described (JER47, JER58) and novel (JER62, JUL32, MAR2, MAR10 and MAR11) cDNAs of the so-called MUC5AC gene are presented and analysed. The data show that in this mucin gene, the tandem repeat domain is interrupted several times with a subdomain encoding a 130 amino acid cysteine-rich peptide in which the TR3A and TR3B peptides previously isolated by Rose et al. [Rose, Kaufman and Martin (1989) J. Biol. Chem., 264, 8193-8199] from airway mucins are found. A consensus peptide sequence for these subdomains involving invariant positions of most of the cysteines is proposed. The consensus nucleotide sequence of this subdomain is also found in the MUC2 gene and in the MUC5B gene, two other mucin genes mapped to 11p15. The functional significance for secreted mucins of these cysteine-rich subdomains and the modular organization of mucin peptides are discussed.

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The core polypeptide of cystic fibrosis tracheal mucin contains a tandem repeat structure. Evidence for a common mucin in airway and gastrointestinal tissue.

Cited by 63 publications

References 23 publications

MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

Monoclonal antibodies reacting with the MUC2 mucin core protein

Characterization of the human mucin gene MUC5AC: a consensus cysteine-rich domain for 11p15 mucin genes?

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