CD44 ISOFORM EXPRESSION MEDIATED BY ALTERNATIVE SPLICING - TISSUE-SPECIFIC REGULATION IN MICE

CD44 is a widely distributed cell surface glycoprotein which shows het erogeneity in molecular expression as a result of post-translational m odification as well as alternative splicing of CD44 mRNA. Functional s tudies have indicated that CD44 plays a role as an adhesion molecule a nd that different CD44-expressing cells differ in their capacities for CD44-dependent ligand binding. These observations have raised the pos sibility that structural modifications of CD44, including those result ing from alternatively spliced mRNA isoforms, are involved in the func tional heterogeneity of CD44. To assess the expression of CD44 isoform s in the mouse, we examined CD44 cDNA by reverse transcription polymer ase chain reaction (RT-PCR). Southern blotting of PCR products with a CD44 cDNA probe or with internal oligonucleotides revealed the express ion in mouse tumor cell lines and normal tissues of multiple CD44 mRNA products which are larger than that observed in the absence of variab le exon expression. Interestingly, different mouse tissues, including lymphoid cells, showed unique patterns of alternative CD44 mRNA in Sou thern blotting analysis. The use of exon-specific primers allowed dete ction of multiple alternatively spliced mRNA species involving express ion of at least seven variable exons. Cloning and sequencing of these PCR products revealed sequence identity with recently identified genom ic CD44 sequences and confirmed that the PCR products correspond to ma ture mRNA expressing alternatively spliced CD44 exons. Taken together, these findings demonstrate that the mouse expresses multiple variably spliced CD44 isoforms and that expression is regulated in a tissue- a nd cell-type specific manner.