Use of mononuclear precursor cells to insert allogeneic genes into growing mouse muscles

Abstract

Our long-term aim is to use allografts of normal muscle precursor cells to insert donor myonuclei, containing a normal genome, into the growing defective muscle fibers of young animals with inherited myopathies. In the present article, we have used isoenzyme variants of glucose-6-phosphate isomerase (GPI) as genetic markers of host and donor genomes in the mouse. We show that mononucleated cells, prepared by enzymatic disaggregation of neonatal donor muscle, 39 can be used to introduce donor GPI genes into muscle fibers of growing muscles of young hosts. The expression of both donor and host GPI genes in the resulting mosaic muscle fibers leads to the formation of a "hybrid" GPI isoenzyme dimer. Such hybrid GPI was found in 10 of 102 host muscles examined. Our results indicate that grafts of muscle precursor cells can be used to alter the genetic constitution of both normal and mildly myopathic muscle.