Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive X-linked neuromuscular disease, for
which there is no cure or therapy. Arising in adult males, it is phenotypically characterized by proximal limb and
bulbar muscle weakness, fasciculations, and muscle atrophy, caused by dysfunction and degeneration of lower
motor neurons and skeletal muscle. The purpose of this project is to generate a more cost-effective, high-
throughput, and disease relevant in vivo model system of SBMA, using zebrafish. Support for zebrafish as a
disease relevant model of SBMA includes the high structural homology of human and zebrafish neuroanatomy
and muscle physiology. Moreover, zebrafish, unlike their small research animal counterparts, flies and worms,
express an androgen receptor (AR), and this AR is similar in structure and function to human AR, indicating
that the zebrafish, in addition to the fact that it is a vertebrate, would serve as a superior high-throughput model
of SBMA. As the disease causing mutation in SBMA is a polyglutamine expansion in the AR protein, we aim to
generate a transgenic lines of zebrafish that express polyglutamine-expanded AR, as well as the control,
normal glutamine length AR. We postulate that male zebrafish expressing polyglutamine-expanded AR will
manifest motor function deficits and histopathology similar to those observed in mouse models and SBMA
patients. A zebrafish model of SBMA would provide a powerful, inexpensive, vertebrate model to complement
current animal models and expedite therapeutic development for this patient population.