Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder.
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Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder. / Rünker, Annette E; Kobsar, Igor; Fink, Torsten; Loers, Gabriele; Tilling, Thomas; Putthoff, Peggy; Wessig, Carsten; Martini, Rudolf; Schachner, Melitta.
In: J CELL BIOL, Vol. 165, No. 4, 4, 2004, p. 565-573.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder.
AU - Rünker, Annette E
AU - Kobsar, Igor
AU - Fink, Torsten
AU - Loers, Gabriele
AU - Tilling, Thomas
AU - Putthoff, Peggy
AU - Wessig, Carsten
AU - Martini, Rudolf
AU - Schachner, Melitta
PY - 2004
Y1 - 2004
N2 - Mutations in the gene of the peripheral myelin protein zero (P0) give rise to the peripheral neuropathies Charcot-Marie-Tooth type 1B disease (CMT1B), Déjérine-Sottas syndrome, and congenital hypomyelinating neuropathy. To investigate the pathomechanisms of a specific point mutation in the P0 gene, we generated two independent transgenic mouse lines expressing the pathogenic CMT1B missense mutation Ile106Leu (P0sub) under the control of the P0 promoter on a wild-type background. Both P0sub-transgenic mouse lines showed shivering and ultrastructural abnormalities including retarded myelination, onion bulb formation, and dysmyelination seen as aberrantly folded myelin sheaths and tomacula in all nerve fibers. Functionally, the mutation leads to dispersed compound muscle action potentials and severely reduced conduction velocities. Our observations support the view that the Ile106Leu mutation acts by a dominant-negative gain of function and that the P0sub-transgenic mouse represents an animal model for a severe, tomaculous form of CMT1B.
AB - Mutations in the gene of the peripheral myelin protein zero (P0) give rise to the peripheral neuropathies Charcot-Marie-Tooth type 1B disease (CMT1B), Déjérine-Sottas syndrome, and congenital hypomyelinating neuropathy. To investigate the pathomechanisms of a specific point mutation in the P0 gene, we generated two independent transgenic mouse lines expressing the pathogenic CMT1B missense mutation Ile106Leu (P0sub) under the control of the P0 promoter on a wild-type background. Both P0sub-transgenic mouse lines showed shivering and ultrastructural abnormalities including retarded myelination, onion bulb formation, and dysmyelination seen as aberrantly folded myelin sheaths and tomacula in all nerve fibers. Functionally, the mutation leads to dispersed compound muscle action potentials and severely reduced conduction velocities. Our observations support the view that the Ile106Leu mutation acts by a dominant-negative gain of function and that the P0sub-transgenic mouse represents an animal model for a severe, tomaculous form of CMT1B.
M3 - SCORING: Zeitschriftenaufsatz
VL - 165
SP - 565
EP - 573
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 4
M1 - 4
ER -
