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Am J Physiol Gastrointest Liver Physiol (January 15, 2003). doi:10.1152/ajpgi.00326.2002
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Submitted on August 6, 2002
Accepted on January 8, 2003

Novel MUC1 splice variants contribute to mucin over-expression in CFTR deficient mice

A. Marina Hinojosa-Kurtzberg1, Malin E. V. Johansson2, Cathy S. Madsen1, Gunnar C. Hansson2, and Sandra J. Gendler1*

1 Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
2 Department of Medical Biochemistry, Goteborg University, 413 90 Gothenburg, Sweden

* To whom correspondence should be addressed. E-mail: gendler.sandra{at}mayo.edu.

A CF mouse expressing the human MUC1 transgene (CFM mice) reverted the CF/Muc1-/- phenotype (little mucus accumulated in the intestine) to that of CF mice expressing mouse Muc1, which exhibited increased mucus accumulation. Western blots and immunohistochemical analysis showed that the MUC1 protein was markedly increased in CFM mice where it was both membrane bound and secreted into the intestinal lumen. Studies to determine the reason for increased levels of the extracellular domain of MUC1 mucin identified mRNA and protein of two novel splice variants and the previously described splice variant MUC1/SEC (lacking the cytoplasmic tail). The novel MUC1 splice variants, CT80 and CT58, were both transmembrane proteins with cytoplasmic tails different from the normal MUC1. The MUC1-CT80 and MUC1/SEC forms are expressed mainly in the CFM intestines. Thus, MUC1 expression is increased and it appears that alternate cytoplasmic tails may change its role in signaling. MUC1 could be an important contributor to the CF intestinal phenotype.




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