Autoradiographic analysis of altered glycosaminoglycan synthesis in the epiphyseal cartilage of neonatal brachymorphic mice.

Brachymorphic (bm/bm) mice are disproportionately short in stature. Past biochemical studies on neonatal mice (Orkin et al., '76) demonstrated that epiphyseal cartilage from these mutants synthesizes glycosaminoglycans (GAG) that are undersulfated. In this study, synthesis of GAG, as determined autoradiographically with Na2 35SO4 and 3H-glucosamine was reduced in all areas of bm/bm epiphyses both in vivo and in vitro as compared to normal C57BL/6J mice. Incorporation of both isotopic precursors into GAG of the brachymorphic proliferative zone was reduced to a greater extent than in the reserve zone. In addition, incorporation of these precursors into GAG of epiphyseal cartilages in vitro, as determined biochemically, was reduced by 40%. In contrast, the incorporation of 3H-leucine and 3H-proline into protein did not show differences between mutant and normal epiphyses. These results suggest that alterations in GAG synthesis in bm/bm epiphyseal growth plates are not exclusive to any one zone, but do appear to be most pronounced in the proliferative zone.