Short tandem repeat sequences in the mammalian genome are considered t
o be unstable, since many of them are polymorphic in length; however,
the extent of this instability has been difficult to quantitate. We ha
ve directly determined the rate of mutation of a simple sequence repea
t in a mammalian cell line. A plasmid containing a dinucleotide repeat
[poly(CA/GT)] that disrupts the reading frame of a downstream gene wa
s integrated into the genome of a mouse cell line, and spontaneous rev
ertants were selected. Reversion rates were more than 100 times higher
in cells carrying the repeated sequence than in control cells that ca
rried the same fusion gene with a 4-bp out-of-frame deletion. Revertan
t clones derived from the lines carrying the dinucleotide repeat had i
nsertions or deletions of one or more repeat units.