Hereditary Spastic Paraplegias (HSPs) are a family of disorders characterized by lower limb paralysis due to failure of development or degeneration of the upper motor neurons. Over 48 genes have been associated with various HSPs with 17 proteins putatively characterized.
An insertion point mutation in one such protein, Maspardin, leads to a premature stop codon and presumably loss of function. A knockout mouse has been generated to better understand the normal function of Maspardin as well as disease pathogenesis. Maspardin is ubiquitously expressed across tissues and has been associated with protein trafficking and signaling. Loss of Maspardin leads to increased axonal branching in vivo. Therefore, Maspardin appears to be a negative regulator of growth factor signaling. Indeed EGFR and BMPR degradation is delayed in knockout cells, compared to normal, following ligand stimulation.
Interestingly other HSP proteins are thought to be growth factor inhibitors as well suggesting a possible common pathway that when disrupted leads to disease.
Dr. Michael C. Hanna, Ph.D.
Department of Biological and Environmental Sciences
Office: STC Rm 261; Laboratory: STC Rm 227, 256
2600 S. Neal St.
Commerce, TX. 75428-3011
Phone: (903) 468-6064
Fax: (903) 886-5997