MOLECULAR-CLONING OF THE AMINO-TERMINAL REGION OF A RAT MUC-2 MUCIN GENE HOMOLOG - EVIDENCE FOR EXPRESSION IN BOTH INTESTINE AND AIRWAY

To obtain cDNAs for analysis of mucin gene transcription in rat models of human disease, we screened a rat intestinal cDNA library in lambda ZAPII using an upstream non-tandem repeat cDNA fragment of the human MUC 2 gene (Gum, J., Hicks, J., Toribara, N., Rothe, E., Lagace, R., a nd Y., K. (1992) J. Biol. Chem. 267, 21375-21383). Three cDNAs, 1-1, 8 -1, and 21-1, were isolated. A translation start site was found in cDN A 21-1. Combined nucleotide sequence for the three cDNAs contained an open reading frame spanning 4546 base pairs. This amino-terminal seque nce contains a non-tandem repeat domain enriched in cysteine (1391 res idues) followed by an irregular tandem repeat domain (122 residues). I dentity with the human gene is about 80% in the non-tandem repeat doma in and about 38% in the irregular tandem repeat domain. Primer extensi on and S1 nuclease protection analysis indicate a transcription start site at 28 base pairs upstream of translation initiation. Northern ana lysis showed expression of cognate RNA in the intestine and airway but not heart and spleen. The cDNAs have been used to isolate the gene pr omoter, the structure of which should yield clues to the regulation of mucin expression in rat models of human disease.