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Vol. 273, Issue 2, 881-890, January 9, 1998

Human Mucin Genes MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 Express Stable and Extremely Large mRNAs and Exhibit a Variable Length Polymorphism
AN IMPROVED METHOD TO ANALYZE LARGE mRNAs

Virginie Debailleul, Anne Laine, Guillemette Huet^§¶, Pascal Mathon^¶, Maud Collyn d'Hooghe, Jean Pierre Aubert^§, and Nicole Porchet^§¶

From the  Unité INSERM U 377, Laboratoire Gérard Biserte and  Unité INSERM U 124, place de Verdun, 59045 Lille Cedex, France, the ^§ Laboratoire de Biochimie et Biologie Moléculaire de l'Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Lille and ^¶ Faculté de Médecine, Université de Lille II, 59037 Lille Cedex, France

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.

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