V Debailleul

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (6)31.52 Total impact

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    ABSTRACT: Alterations in the structure and/or quantity of mucins could alter the barrier function of mucus and play a role in initiating and maintaining mucosal inflammation in Crohn's disease. To investigate the hypothesis of a mucin gene defect in Crohn's disease, we analyzed the expression of the different mucin genes in the ileal mucosa of patients with Crohn's disease and controls. mRNA expression levels were assessed by a quantitative dot blot analysis and compared (i) between healthy and involved ileal mucosa of patients with Crohn's disease and (ii) between healthy mucosa of patients with Crohn's disease and controls. Expression of the different mucin genes was heterogeneous among controls and patients with Crohn's disease, except for MUC6 in controls. Nevertheless, MUC1 mRNA expression was significantly decreased in the involved ileal mucosa of patients with Crohn's disease when compared to the healthy mucosa (p = 0.02). Moreover, the expression levels of MUC3, MUC4, and MUC5B were significantly lower in both healthy and involved ileal mucosa of patients with Crohn's disease compared to controls (p < or = 0.05). The decrease of expression levels of some mucin genes (more particularly MUC3, MUC4, and MUC5B) in both healthy and involved ileal mucosa suggests a primary or very early mucosal defect of these genes in CD.
    Inflammatory Bowel Diseases 03/1999; 5(1):24-32. · 5.12 Impact Factor
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    ABSTRACT: Of the nine mucin genes that have been characterized, only MUC1 and MUC7 have been fully sequenced, and their transcripts can be detected as distinct bands of predicted size by Northern blot analysis. In contrast, the RNA patterns observed for each of the other MUC genes have usually shown a very high degree of polydispersity. This polydispersity has been believed to be one of the typical features of the mucin mRNAs, but until now, its origin has remained unexplained. In the work described in the present paper, we investigated two possible kinds of explanation for this phenomenon: namely that the extensive polydispersity results from a biological mechanism or that it is artifactual in origin. The data obtained, as a result of improving the purification and blotting methods, allowed us to show that in all of the tissues analyzed, each of the genes, MUC2-6, expresses mRNAs that are stable and are of an unusually large size to be found in eukaryotes (14-24 kilobases). Moreover, allelic variations in length of these mucin transcripts were observed. We demonstrate that these variations are directly related to the variable number of tandem repeat polymorphisms seen at the DNA level.
    Journal of Biological Chemistry 02/1998; 273(2):881-90. · 4.65 Impact Factor
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    ABSTRACT: Of the nine mucin genes that have been characterized, only MUC1 and MUC7 have been fully sequenced, and their transcripts can be detected as distinct bands of predicted size by Northern blot analysis. In contrast, the RNA patterns observed for each of the other MUC genes have usually shown a very high degree of polydispersity. This polydispersity has been believed to be one of the typical features of the mucin mRNAs, but until now, its origin has remained unexplained. In the work described in the present paper, we investigated two possible kinds of explanation for this phenomenon: namely that the extensive polydispersity results from a biological mechanism or that it is artifactual in origin. The data obtained, as a result of improving the purification and blotting methods, allowed us to show that in all of the tissues analyzed, each of the genes, MUC2–6, expresses mRNAs that are stable and are of an unusually large size to be found in eukaryotes (14–24 kilobases). Moreover, allelic variations in length of these mucin transcripts were observed. We demonstrate that these variations are directly related to the variable number of tandem repeat polymorphisms seen at the DNA level.
    Journal of Biological Chemistry 01/1998; 273(2):881-890. · 4.65 Impact Factor
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    ABSTRACT: In recent years considerable advances have been made in our knowledge of human mucin genes. Although analysis of their genomic organization is still in progress, the pattern of their expression in different human mucosae is now fairly well established. However, little is known about their expression in the biliary tree. In this study we determined the pattern of expression of the different human mucin genes in gallbladder biliary epithelial cells, intrahepatic bile ducts and liver. Two complementary methods were used: Northern-blot and in situ hybridization analyses. The experiments were performed with eight probes corresponding to MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7. Our results revealed a strong mRNA expression of MUC3, MUC6 and MUC5B, a weak expression of MUC1, MUC5AC and MUC2, and no expression of MUC4 and MUC7. Surprisingly, MUC3, which was the gene which was most expressed in the biliary tree, was also found in hepatocytes, suggesting another function for the MUC3 protein than that of a secreted mucin. We conclude that MUC3, MUC6 and MUC5B were the main mucin genes expressed in biliary epithelial cells.
    Journal of Hepatology 01/1998; 27(6):1057-66. · 9.86 Impact Factor
  • Biochemical Society Transactions 12/1995; 23(4):800-5. · 2.59 Impact Factor
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    ABSTRACT: 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.
    Biochemical Journal 02/1995; 305 ( Pt 1):211-9. · 4.65 Impact Factor