A Mouse Model of a Human Motor Neuron Disease
Chen Lai, Xian Lin, Jayanth Chandran, Hoon Shim, Wan-Jou Yang, and Huaibin Cai

Motor neurons are particularly vulnerable to problems in cargo transport along axons. This job is handled in the anterograde direction by kinesin and in the retrograde direction by the dynein/dynactin complex. This week, Lai et al. focused on dynactin P150glued, which is part of the dynactin complex that binds to microtubules and dynein and thus facilitates retrograde transport. A mutation in P150glued, G59S, has been linked to a familial form of motor neuron disease. The authors created a knock-in mouse model of this mutation, as well as heterozygous P150glued knock-out mice. The heterozygous knock-out mice were normal, but heterozygous knock-in mice had loss of motor neurons, gait abnormalities, and accumulations of neurofilaments and synaptic vesicles proteins at the neuromuscular junction. The results confirm the role of P150glued in retrograde transport and are consistent with the clinical picture of humans with this mutation.


http://www.eurekalert.org/pub_releas...-ntf121207.php