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We report here that joint inflammation in collagen-induced arthritis is more aggravated in CD44-knockout mice than in WT mice, and we provide evidence for molecular redundancy as a causal factor. Furthermore, we show that under the inflammatory cascade, RHAMM (receptor for hyaluronan-mediated motility), a hyaluronan receptor distinct from CD44, compensates for the loss of CD44 in binding hyaluronic acid, supporting cell migration, up-regulating genes involved with inflammation (as assessed by microarrays containing 13,000 cDNA clones), and exacerbating collagen-induced arthritis. Interestingly, we further found that the compensation for loss of the CD44 gene does not occur because of enhanced expression of the redundant gene (RHAMM), but rather because the loss of CD44 allows increased accumulation of the hyaluronic acid substrate, with which both CD44 and RHAMM engage, thus enabling augmented signaling through RHAMM. This model enlightens several aspects of molecular redundancy, which is widely discussed in many scientific circles, but the processes are still ill defined.

Original publication

DOI

10.1073/pnas.0407378102

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

13/12/2004

Volume

101

Pages

18081 - 18086

Addresses

The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

Keywords

Animals, Mice, Knockout, Mice, Arthritis, Disease Models, Animal, Inflammation, Collagen, Hyaluronic Acid, Antigens, CD44, Extracellular Matrix Proteins, DNA, Complementary, Blotting, Western, Oligonucleotide Array Sequence Analysis, Flow Cytometry, Crosses, Genetic, Cell Movement, Up-Regulation, Transgenes, Time Factors, Female, Male