Spinal cord-specific deletion of the glutamate transporter GLT1 causes motor neuron death in mice

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder characterized by the selective loss of motor neurons. The precise mechanisms that cause the selective death of motor neurons remain unclear, but a growing body of evidence suggests that glutamate-mediated excitotoxicity has been considered to play an important role in the mechanisms of motor neuron degeneration in ALS. Reductions in glutamate transporter GLT1 have been reported in animal models of ALS and the motor cortex and spinal cord of ALS patients. However, it remains unknown whether the reduction in GLT1 has a primary role in the induction of motor neuron degeneration in ALS. Here, we generated conditional knockout mice that lacked GLT1 specifically in the spinal cord by crossing floxed-GLT1 mice and Hoxb8-Cre mice. Hoxb8-Cre/GLT1flox/flox mice showed motor deficits and motor neuron loss. Thus, loss of the glial glutamate transporter GLT1 is sufficient to cause motor neuron death in mice. •GLT1 deletion in spinal cord causes motor deficits.•GLT1 deletion in spinal cord induces spinal motor neuron loss.•GLT1 deletion in spinal cord induces gliosis in the ventral horn.