Sexual dimorphism in disease onset and progression of a rat model of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing the progressive loss of brain and spinal cord motor neurons. The exact etiology of ALS is still uncertain, but males have consistently been shown to be at a higher risk for the disease than females. Recently, transgenic rats overexpressing mutant forms of the human SOD1 (hSOD1) gene have been established as a valuable disease model of ALS. Here we show that sexual dimorphism in disease onset is also observed in hSOD1G93A transgenic rats. Disease onset was consistently earlier in male than in female hSOD1G93A rats. We also found that hSOD1G93A male rats lost weight more rapidly following disease onset compared to hSOD1G93A females. Furthermore, we tested locomotor function using the Basso-Beattie-Bresnahan (BBB) rating scale and a beam walking test. We found that motor dysfunction started earlier in males than in females but progressed similarly in the two sexes. These results have important implications for future experimentation and therapeutic development using the rat model of ALS.