This proposal is aimed at fully characterizing our mouse model of Spinal Bulbar Muscular Atrophy (SBMA).SBMA is a X-linked lower motor neuron disease characterized by adult onset muscle weakness, atrophy,and significant depletion of motoneurons. It has been assumed that muscle weakness and atrophy resultfrom loss of innervation from motoneurons. Our mouse model suggests 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 us to directly examine the previously unsuspected role of ARin muscle fibers in initiating SBMA. The proposed experiments are aimed at testing the hypothesis that ARsin skeletal muscle fibers trigger SBMA. This proposal may also impact other neurodegenerative diseases,such as Amyotrophic Lateral Sclerosis (ALS) which may also originate in the muscle instead of themotorneurons.
| Johansen, Jamie A; Troxell-Smith, Sandra M; Yu, Zhigang et al. (2011) Prenatal flutamide enhances survival in a myogenic mouse model of spinal bulbar muscular atrophy. Neurodegener Dis 8:25-34 |
| Johansen, Jamie A; Yu, Zhigang; Mo, Kaiguo et al. (2009) Recovery of function in a myogenic mouse model of spinal bulbar muscular atrophy. Neurobiol Dis 34:113-20 |
| Monks, Douglas Ashley; Rao, Pengcheng; Mo, Kaiguo et al. (2008) Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy. Horm Behav 53:729-40 |
| Monks, Douglas Ashley; Johansen, Jamie A; Mo, Kaiguo et al. (2007) Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease. Proc Natl Acad Sci U S A 104:18259-64 |
