Disruption of Egr2–Nab2 Interaction Reduces Myelination

[Guest guest]

4. Disruption of Egr2–Nab2 Interaction Reduces Myelination

http://www.eurekalert.org/pub_releases/2009-02/sfn-ntf021809.php

H. Baloh, Amy Strickland, Ryu, Nam Le,

Fahrner, Mao Yang, Rakesh Nagarajan, and Milbrandt

Charcot–Marie–Tooth (CMT) disease is a group of inherited peripheral

neuropathies caused by different genetic mutations and characterized

by muscle weakness in the lower limbs.

Baloh et al. have created a mouse model of CMT type 4E by knocking in

a causative mutation—a point mutation in the transcription factor

Egr2—in transgenic mice. Egr2, together with a coregulatory protein,

Nab2, is required for expression of genes involved in myelination.

The point mutation prevented the association between Nab2 and Egr2,

and therefore reduced transcription of Egr2 target proteins. Like

patients, mutant mice developed a hypomyelinating neuropathy.

The mice appeared normal at birth, but muscle weakness appeared ~14 d

later and progressed rapidly, leading to paralysis and death within

4 & #55312; & #56517; d. Myelination was reduced, and action potentials slowed

and/or

failed to propagate to the nerve terminal. Axons did not degenerate,

however, indicating that profound motor defects can be produced by

myelin loss alone, without secondary axonal degeneration.