STABILITY OF AN EXPANDED TRINUCLEOTIDE REPEAT IN THE ANDROGEN RECEPTOR GENE IN TRANSGENIC MICE

The expansion of trinucleotide repeat sequences underlies a number of hereditary neurological disorders. To study the stability of a trinucl eotide repeat and to develop an animal model of one of these disorders , spinal and bulbar muscular atrophy (SBMA), we have generated transge nic mice carrying either the normal or expanded repeat human androgen receptor (AR) gene. Unlike the disease allele in humans, the AR cDNA c ontaining the expanded repeat in transgenic mice showed no change in r epeat length with transmission. Expression of the SBMA AR was,found in transgenic mice, but at a lower level than normal endogenous expressi on. The lack of a physiological pattern of expression may explain why no phenotypic effects of the transgene were observed.