MUSCLE UNDERGOES ATROPHY IN ASSOCIATION WITH INCREASE OF LYSOSOMAL CATHEPSIN ACTIVITY IN INTERLEUKIN-6 TRANSGENIC MOUSE

Interleukin(IL)-6 transgenic mice were produced by microinjection of h uman IL-6 cDNA fused with H-2L(d) promotor into the pronucleus of fert ilized eggs from C57BL/6J mice. At 16 weeks old, the gastrocnemius mus cles of the IL-6 transgenic mice became atrophic as compared to those of the normal mice, while the body weights increased significantly. Th e activities and mRNA levels of lysosomal cathepsins B and L were incr eased in the muscles of the transgenic mice. Immunohistochemical study on the muscles showed increased staining of both cathepsins B and L i n the transgenic mice. IL-6 is responsible for enhanced muscle catabol ism by activating the lysosomal cathepsin (B and L) system. (C) 1995 A cademic Press, Inc.