Expression of a Specific Subset of CD44 Variant Transcripts in NOD Pancreatic Islets

Abstract

Adhesion of lymphocytes to the endothelial venules inside the islets of Langerhans seems to initiate the infiltration of islets in NOD mice. An overexpression of the lymphocyte surface molecule CD44 in infiltrated NOD islets compared with peripheral blood lymphocytes was recently reported. The CD44 protein family includes a variety of molecules generated by alternative RNA splicing from 10 variant exons (v1-v10). By using reverse transcriptase-polymerase chain reaction followed by Southern blotting and hybridization to exon-specific cDNA probes, we investigated the expression of CD44 isoforms in highly purified islets of Langerhans from 4- and 10-week-old NOD mice. At least six CD44 isoforms were strongly overexpressed in NOD islets at 4 and 10 weeks when compared with age-matched BALB/c islets. Controls in different tissues indicate that these variants are specifically increased in the islets from the NOD strain. Islets from the NOD-scid/scid strain also expressed these variant exons. Splenocytes from BALB/c did not express CD44 isoforms, whereas splenocytes from 4-week-old NOD mice did express CD44 variants. Treatment with inflammatory mediators induced new isoforms; however, these transcripts have a different variant exon composition from that found in NOD mice islets. These results suggest that some isoforms are expressed very early in the development of insulitis by a component of the NOD islet itself and underscore a possible role of CD44 in islet infiltration.

Abrogation of Experimental Colitis Correlates with Increased Apoptosis in Mice Deficient for Cd44 Variant Exon 7 (Cd44v7)

“…Analyses of surface molecules from inflamed regions of patients or mice with Th1-type autoimmune disease or chronic inflammations, such as systemic lupus erythematosus, rheumatoid arthritis, experimental autoimmune encephalomyelitis, insulin-dependent diabetes mellitus, and delayed-type hypersensitivity reactions all correlate with high expression levels of CD44 (43)(44)(45)(46)(47). Using CD44 reagents specific for the variant isoforms, disease scores in experimental autoimmune encephalomyelitis could be strongly reduced (48).…”

Daniel H. Mintz (1930–2020): An Extraordinary Physician-Scientist and a Pioneer in Islet Transplantation

“…Dan also recruited Alex Rabinovitch, with whom he developed islet cell culture methods, explored the potential for β-cell replication, and studied various aspects of β-cell biology (11)(12)(13)(14)(15). He later recruited Ricardo Pastori, and together they employed molecular biology approaches to identify CD44 isoforms involved in the migration of lymphocytes to the islets in nonobese diabetic mice (16).…”