Light microscopy, including immunohistochemical techniques, and electron microscopy were performed on epiphyseal growth cartilage from brachymorphic (bm/bm) mice and age-matched phenotypically normal siblings aged 5, 16 and 25 days. In the bm/bm mice light microscopy showed a disturbed columnar arrangement and numerous chondrocytes with pronounced regressive changes. The normal development of proliferative cells into hypertrophic cells was halted and thus only a rather small and ill-defined hypertrophic zone was seen. The calcifying zone was irregular and the normal lacunae were replaced by a densely staining matrix. Using immunofluorescence techniques, the presence of considerable amounts of both type II and type V collagen was demonstrated in the bm/bm mice, while the cartilage from controls contained only type II. Ultrastructurally the lacunar matrix contained bundles of fine fibrils without the typical collagen periodicity which might indicate synthesis of a defective procollagen. Our observations together with the previously demonstrated deficiency of 3'-phosphoadenosine 5'-phosphosulphate, illustrate the complexity of the growth cartilage disturbance in the bm/bm mouse. Most of our findings are at variance with those described in the literature and possible pathogenetic mechanisms for the observed alterations in the growth cartilage are discussed.
