Persia Mirkazemi

Skeletal muscle injury results in satellite cell activation, proliferative self-renewal, and differentiation into myogenic cells that are primed to fuse into damaged muscle fibers. The regulatory mechanisms specifying rates of self-renewal are poorly understood. We have identified a DNA segment bearing a genetic modifier that distinguishes satellite cell self renewal on the C57BL/6 background (rapid) from DBA/2 (slow). We have backcrossed this modifier from B6 onto DBA for 14 generations and made it homozygous. Here we show that satellite cells from the congenic proliferate more rapidly than those of DBA/2 mice. Differentiation propensity, elucidated by fusion index of MHC+ cells, was not affected. Transplantation assays showed that the cells of the congenic had greater engraftment potential, elicited by the number of dystrophin-+ muscle fibers into dystrophin-deficient NSG-mdx4Cv mice. This data suggests that we have identified a modifier gene responsible for some of the large variance in the satellite cell phenotype between C57BL/6 and DBA/2 mice.