Abstract
Patients with PMP22 deficiency present with focal sensory and motor deficits when peripheral nerves are stressed by mechanical force. It has been hypothesized that these focal deficits are due to mechanically induced conduction block (CB). To test this hypothesis,weinduced 60-70% CB (defined by electrophysiological criteria) by nerve compression in an authentic mouse model of hereditary neuropathy with liability to pressure palsies (HNPP) with an inactivation of one of the two pmp22 alleles ( pmp22+/-). Induction time for the CB was significantly shorter in pmp22+/- mice than that in pmp22+/+ mice. This shortened induction was also found in myelin-associated glycoprotein knock-out mice, but not in the mice with deficiency of myelin protein zero, a major structural protein of compact myelin. Pmp22+/- nerves showed intact tomacula with no segmental demyelination in both noncompressed and compressed conditions, normal molecular architecture, and normal concentration of voltage-gated sodium channels by [3H]-saxitoxin binding assay. However, focal constrictions were observed in the axonal segments enclosed by tomacula, a pathological hallmark of HNPP. The constricted axons increase axial resistance to action potential propagation, which may hasten the induction of CB in Pmp22 deficiency. Together, these results demonstrate that a function of Pmp22 is to protect the nerve from mechanical injury.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 600-608 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience |
| Volume | 30 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 13 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
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Conduction block in PMP22 deficiency. / Bai, Yunhong; Zhang, Xuebao; Katona, Istvan; da Cunha Saporta, Mario; Shy, Michael E.; O'Malley, Heather A.; Isom, Lori L.; Suter, Ueli; Li, Jun.
In: Journal of Neuroscience, Vol. 30, No. 2, 13.01.2010, p. 600-608.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Conduction block in PMP22 deficiency
AU - Bai, Yunhong
AU - Zhang, Xuebao
AU - Katona, Istvan
AU - da Cunha Saporta, Mario
AU - Shy, Michael E.
AU - O'Malley, Heather A.
AU - Isom, Lori L.
AU - Suter, Ueli
AU - Li, Jun
PY - 2010/1/13
Y1 - 2010/1/13
N2 - Patients with PMP22 deficiency present with focal sensory and motor deficits when peripheral nerves are stressed by mechanical force. It has been hypothesized that these focal deficits are due to mechanically induced conduction block (CB). To test this hypothesis,weinduced 60-70% CB (defined by electrophysiological criteria) by nerve compression in an authentic mouse model of hereditary neuropathy with liability to pressure palsies (HNPP) with an inactivation of one of the two pmp22 alleles ( pmp22+/-). Induction time for the CB was significantly shorter in pmp22+/- mice than that in pmp22+/+ mice. This shortened induction was also found in myelin-associated glycoprotein knock-out mice, but not in the mice with deficiency of myelin protein zero, a major structural protein of compact myelin. Pmp22+/- nerves showed intact tomacula with no segmental demyelination in both noncompressed and compressed conditions, normal molecular architecture, and normal concentration of voltage-gated sodium channels by [3H]-saxitoxin binding assay. However, focal constrictions were observed in the axonal segments enclosed by tomacula, a pathological hallmark of HNPP. The constricted axons increase axial resistance to action potential propagation, which may hasten the induction of CB in Pmp22 deficiency. Together, these results demonstrate that a function of Pmp22 is to protect the nerve from mechanical injury.
AB - Patients with PMP22 deficiency present with focal sensory and motor deficits when peripheral nerves are stressed by mechanical force. It has been hypothesized that these focal deficits are due to mechanically induced conduction block (CB). To test this hypothesis,weinduced 60-70% CB (defined by electrophysiological criteria) by nerve compression in an authentic mouse model of hereditary neuropathy with liability to pressure palsies (HNPP) with an inactivation of one of the two pmp22 alleles ( pmp22+/-). Induction time for the CB was significantly shorter in pmp22+/- mice than that in pmp22+/+ mice. This shortened induction was also found in myelin-associated glycoprotein knock-out mice, but not in the mice with deficiency of myelin protein zero, a major structural protein of compact myelin. Pmp22+/- nerves showed intact tomacula with no segmental demyelination in both noncompressed and compressed conditions, normal molecular architecture, and normal concentration of voltage-gated sodium channels by [3H]-saxitoxin binding assay. However, focal constrictions were observed in the axonal segments enclosed by tomacula, a pathological hallmark of HNPP. The constricted axons increase axial resistance to action potential propagation, which may hasten the induction of CB in Pmp22 deficiency. Together, these results demonstrate that a function of Pmp22 is to protect the nerve from mechanical injury.
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U2 - 10.1523/JNEUROSCI.4264-09.2010
DO - 10.1523/JNEUROSCI.4264-09.2010
M3 - Article
VL - 30
SP - 600
EP - 608
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 2
ER -