X-ray and histological analysis of Novdel3−/− and Novdel3+/+ knee joints. A–C: X-rays of 2, 6 and 12 month male Novdel3−/− joints revealed abnormal bone (B, C, arrowhead), osteophytes (C,*), enlarged epicondyles (C, arrow), whereas male Novdel3+/+ joints were normal. Knee joints of both Novdel3−/− and Novdel3+/+ females were normal (data not shown). D–G: Histological analysis of 2, 6 and 12-month-old Novdel3−/− and Novdel3+/+ females (D, E) and males (F, G) by staining with toluidine blue (D, F) and H and E (E, G). Normal toluidine blue staining of Novdel3−/− females compared with controls (D), but H and E staining showed decreased articular cartilage cell densities at 2, 6 and 12 months (E) with cell remnants (cr) present at 6 and 12 months (E) (see inserts). Compared to age and sex matched controls, Novdel3−/− male joints had reduced toluidine blue staining (F), depleted articular cartilage cell density and articular damage at 6 and 12 months (G) with fibrillation (f) at 6 and 12 months. H: H and E staining of Novdel3−/− and Novdel3+/+ males at 12 months showing significant joint pathology in the mutant with erosion (e), clefts (c), enlarged (em) or damaged (dm) meniscus (m), cruciate ligament (cl) degeneration and fibrocartilage expansion (*) in the joint margins and subchondral sclerosis (ss). I: 12 month males showed distinct subchondral sclerosis (ss) with loss of marrow cavities (mar). tib; tibia, fem; femur, ac; articular cartilage, cc; calcified cartilage, tm; tidemark. Scale bar 1 mm (A–C), 100 μm (D, F, H) and 50 μm (E, G).