Tissue-specific and growth-regulated expression of CD44 variable exon determinants in the mouse

CD44 is a polymorphic transmembrane glycoprotein widely expressed in lymphocytes and epithelial cells. CD44 polymorphism reflects both posttranslational modification and alternative splicing of up to 10 variably expressed exons in the membrane-proximal CD44 extracellular domain. An analysis of CD44 variable exon-containing isoforms in the mouse was carried out by generating a panel of monoclonal antibodies against variable region determinants of CD44. Immunohistochemical analysis demonstrated selective patterns of expression of CD44 variable exon determinants in normal tissues, and flow cytometric analysis identified expression of CD44 variable exon-dependent determinants in epithelial and lymphoid cell lines. Regulation of alternative splicing was studied by characterization of cell surface expression of CD44 variable exon determinants on HC11 mammary epithelial cells, and it was demonstrated that variably spliced isoforms are selectively regulated as a function of growth phase in vitro. These results demonstrate the tissue-specific and growth-regulated expression of the CD44 isoform at the level of cell surface protein products and identify isoform-specific determinants that can be targeted in analysis of isoform-specific function.