Figure 1.

Map of the congenic intervals, and the effect of the Cia5d locus on fibroblast-like synoviocyte (FLS) invasion. A, Markers used in the breeding of DA.ACI(Cia10), DA.F344(Cia4), and DA.F344(Cia5d) rats are shown, along with their respective positions on chromosomes 2, 7, and 10, and genotypes. Numbers inside the bars represent the position in the chromosome (megabases). B, FLS from DA.F344(Cia5d) rats (passage range 6–9 [median 7.5]) had a significant reduction of 86.5% in the median number of invading cells, compared with FLS from DA rats (passage range 6–16 [median 8]). The median number of invading cells from DA.F344(Cia4) rats and that of invading cells from DA.ACI(Cia10) rats were not significantly lower than that for DA rats. (Experiments were performed with BD Matrigel invasion chambers.) * = P ≤ 0.001 versus DA rats, by Mann-Whitney test. C, The increased invasive properties of FLS from DA rats require exposure to pristane, as FLS from naive DA rats have invading properties similar to those of FLS from naive rats and DA.F344(Cia5d) rats with pristane-induced arthritis (PIA). Therefore, F344 alleles at the Cia5d interval render cells resistant to pristane-induced increased invasive properties. (Experiments were performed with Chemicon Matrigel invasion chambers. Samples were run on 2 separate days, and absorbance was normalized according to a set of controls/duplicates run on both days.) * = P = 0.018; # = P = 0.002 versus DA rats with PIA, by Mann-Whitney test. Bars in B and C are the 25th and 75th percentiles. D and E, Ankle joints from DA rats (D) and DA.F344(Cia5d) rats (E) were collected on day 32 after initiation of PIA. Synovial hyperplasia was extensive in DA rats, with cartilage and bone erosion, while synovium in DA.F344(Cia5d) rats was normal, with no erosions (arrows). (Hematoxylin and eosin stained; original magnification × 100.)