CONTRACTILE PROPERTIES OF DIAPHRAGM MUSCLE SEGMENTS FROM OLD MDX AND OLD TRANSGENIC MDX MICE

Diaphragm muscles of young (4- to 6-mo-old) mdx mice show severe fiber necrosis and have normalized forces and powers 60 and 46% of the valu es for control C57BL/10 mice. In contrast, microinjection of mdx mouse embryos with a truncated dystrophin minigene has produced young trans genic mdx (tg-mdx) mice with a level of dystrophin expression and stru ctural and functional properties of diaphragm muscle strips measured i n vitro not different from those of control mice. Whether dystrophin e xpression and functional corrections persist for the life span of thes e animals is not known. We tested the null hypothesis that, in old (24 mo) tg-mdx mice, dystrophin expression is adequate and diaphragm musc le strips have forces and powers not different from values for diaphra gm muscle strips from young tg-mdx mice or control mice. Compared with control values, diaphragm muscle strips from old mdx mice had normali zed forces and powers of 48 and 31%, respectively. Expression of dystr ophin persisted in diaphragm muscles of old tg-mdx mice, and functiona l properties were not different from diaphragm muscles of young tg-mdx or young or old control mice. These results suggest that, with a tran sgenic animal approach, dystrophin expression and functional correctio ns persist for the life span of the animals.