Regulation of muc5 and muc1 gene expression: correlation with
airway mucous differentiation.
Guzman, Karen, Thomas Bader, Paul Nettesheim.
Laboratory of Pulmonary Pathobiology, National Institute of
Environmental Health Sciences, Research Triangle Park, NC 27709
APStracts 3:0010L, 1996.
The purpose of this paper was to obtain probes to study the structure
and function of mucins in rat models of airway cell differentiation
and disease. We report the isolation and characterization of the rat
cDNA homologue of the human airway secretory mucin, MUC5. Further, we
demonstrate the coordinate regulation of the expression of MUC5 and
MUC1 (a membrane-bound mucin) and mucous differentiation. The rat
MUC5 was cloned by the reverse-transcription-polymerase-chain
-reaction using motifs conserved in the secretory mucins, MUC2 and
MUC5. The rat cDNA revealed a high degree of sequence similarity to
human MUC5 (73% at the amino acid level). Alignments with three other
secretory mucins (human MUC5, human MUC2, rat MUC2), indicated a
conservation of the cysteines and of the octapeptide motifs, but a
lack of conservation of a short tandem repeat sequence that is found
only in the human MUC5 Northern analysis of MUC1 and MUC5 indicated a
specific tissue-restricted pattern of expression. Surprisingly, rat
MUC5 exhibited a monodisperse signal, a characteristic that is
unusual for most secretory mucins including the human MUC5.
Expression of MUC1 and MUC5 correlated with mucous differentiation.
Both genes were expressed at undetectable or very low levels in
undifferentiated cultures, but both mucins became strongly expressed
during mucous differentiation. Furthermore, neither mucin gene was
expressed in retinoid-deficient cultures which undergo squamous
instead of mucous differentiation. These studies demonstrate that
expression of MUC1 and MUC5 are coordinately regulated with airway
mucous cell differentiation. These cDNAs should provide useful tools
to study mucin synthesis during differentiation and disease.
Received 8 September 1995; accepted in final form 22 December
1995.
APS Manuscript Number L272-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96