Our lab recently created several transgenic mouse models, in which androgen receptor (AR) gene expression has been manipulated. Uniquely, we have only manipulated AR gene expression in skeletal muscle fibers, using a human skeletal actin promoter. The model that I am studying as the focus of my dissertation over-expresses AR. Originally we developed this mouse model to address questions in the SNB system. Quite unexpectedly, the mice that over-express AR developed a neurodegenerative disease, Spinal Bulbar Muscular Atrophy (SBMA, also known as Kennedy's disease).
SBMA is a heritable X-linked, slowly progressive lower motor neuron disease characterized by adult onset muscle weakness, atrophy, and loss of motoneurons. It has been assumed that muscle weakness and atrophy results from loss of innervation. However, my work demonstrates that, contrary to prevailing theory, SBMA is in fact a myogenic disease. (i.e., the disease is triggered by problems that originate in the muscle, not the motoneurons.) This new model allows me to directly examine the previously unsuspected role of AR in muscle fibers in initiating SBMA. This may also impact other neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS) which may also originate in the muscle instead of the motorneurons.
More on Jamie
- In addition to my graduate work, I have a few hobbies. You can check them out at:
- e-mail: johanse8 [at] msu.edu