A mouse model of spinal and bulbar muscular atrophy

Abstract

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease, caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen receptor (AR) gene. This disorder is characterized by degeneration of motor and sensory neurons, proximal muscular atrophy, and endocrine abnormalities, such as gynecomastia and reduced fertility. We describe the development of a transgenic model of SBMA expressing a full-length human AR (hAR) cDNA carrying 65 (AR65) or 120 CAG repeats (AR120), with widespread expression driven by the cytomegalovirus promoter. Mice carrying the AR120 transgene displayed behavioral and motor dysfunction, while mice carrying 65 CAG repeats showed a ..