Huntington's Disease transgenic mice were used for an exploration into the stability of a trinucleotide repeat. The brain shows heterogeneous somatic instability that increases quantitatively with age. To test somatic CAG-repeat alterations during long-term culture, DNA was extracted from transgenic tissue, primary fibroblasts, and SV40-immortalized fibroblasts at intervals of approximately 100 cell doublings. In fibroblasts derived from an adult mouse, there was an initial short truncation of the repeat, followed by an emerging population of cells showing continuous slow expansion. After 15 months in continuous culture (approximately 600 cell doublings following transformation) the major CAG peak has increased from 155 to approximately 170 triplets. This in vitro system can now be used to assay factors that affect instability.
Copyright 1999 Elsevier Science B.V.