Osteopontin (OPN), also called early T cell activation gene-1 (Eta-1) or secreted phosphoprotein 1 (Spp1), has important functions in bone metabolism (1, 2) and in inflammation and immunity to infectious diseases (3, 4). Recently, several studies (5–9) have suggested that OPN also plays a crucial role in inflammatory disease models of multiple sclerosis (MS) and rheumatoid arthritis (RA). Chabas et al.(5) first suggested OPN involvement in MS, based on both expression analysis data from MS-affected brains and from studies of mice with the OPN gene deleted; those mice were shown to be partly protected from experimental autoimmune encephalomyelitis (EAE). This was followed up by several papers using other models for RA and MS (8, 9).

The flaw in these data is that they may be explained by linked polymorphic genes, because the mice were not fully backcrossed and typed in these experiments. We have deleted the OPN gene using homologous recombination of strain 129–derived cells, and have subsequently backcrossed it to the C57/BL10 strain with a congenic major histocompatibility complex (MHC) fragment of the q haplotype (B10. Q), which is usually susceptible to EAE, collagen induced arthritis (CIA), and anti-CII antibody transfer induced arthritis (CAIA)(10–12). The gene was shown to be completely inactivated, with no aberrant transcript. The mice were backcrossed for 12 generations to the C57/Black background, and the remaining linked fragment was determined with microsatellite marker [between positions 45 and 64 centiMorgan (cM) on chromosome 5]. In all experiments, both wild-type B10. Q littermates and heterozygous littermates were used as controls. In contrast to the findings published by Chabas et al.(5) and others, we saw no effect on any inflammatory model tested—EAE, CIA, or CAIA (Table 1). In our EAE experiments we used 25 g recombinant rat myelin oligodendrocyte glycoprotein (MOG) emulsified in complete Freund’s adjuvant (CFA) using a 0-to-8 scoring scale, as described in detail in (10). The mice were followed for 37 days, and 20% of them were in remission at the end of the experiment. A direct comparison with previously published experiments shows that our exper-