DECREASE IN CELLULAR REPLICATIVE POTENTIAL IN GIANT MICE TRANSFECTED WITH THE BOVINE GROWTH-HORMONE GENE CORRELATES TO SHORTENED LIFE-SPAN

Adult mice, (C57BL/6 x Sjl)F1 hybrids, transfected with the bovine gro wth hormone gene (bGH) grow to twice normal size, but have a mean life span less than 50% that of control siblings without the transgene. Th e replicative potentials of cells from six different tissue sites (tai l skin and ear skin dermal fibroblasts, tail subdermal connective tiss ue fibroblasts, kidney medulla epithelial cells, bone marrow myofibrob lasts, and spleen myofibroblasts) were assayed in vitro using clone si ze distribution analysis. Cells from all of the above bGH+ tissues pro duced a smaller fraction of large clones, relative to age-matched cont rols, in all of these cell types. The loss of replicative potential di d not appear to be the result of negative conditioning of the cloning media by the bGH+ cells, and was tightly correlated to the period of a ccelerated growth in these animals (3-12 weeks), a time when additiona l GH receptors are expressed. (C) 1993 Wiley-Liss, Inc.