Premature ageing in transgenic mice expressing different growth hormone genes

Abstract

Transgenic mice expressing various growth hormone genes have markedly reduced life spans, with few animals surviving beyond 12 months in some of the lines. Except for an increased incidence of mammary tumours in female mice expressing human growth hormones, pathological findings in debilitated or moribund transgenic mice resemble the well-documented degenerative changes that occur at a much greater chronological age in normal rodents. This study demonstrates that 10-month-old male transgenic mice expressing bovine growth hormone (known as 25-copy PEPCK. bGH transgenic mice) also show age-related changes in hypothalamic and striatal neurotransmitter metabolism that are not seen in normal litter mate controls until at least 24 months of age. Female mice and male mice with a lower circulating concentration of bGH (known as 5-copy PEPCK. bGH transgenic mice) live longer and fail to show the same magnitude of change in neurotransmitter synthesis and release. Although more work needs to be done to determine the physiological significance of these changes and to determine their relationship to the general effects of ageing on the CNS, transgenic mice expressing various growth hormone genes may provide an interesting and valuable model with which to study the ageing process.