Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.

We have identified and characterized a new peripheral myelin protein 22 (Pmp22) mouse mutant. The mutation results in a serine to threonine amino acid substitution at residue 72, which is a hot spot for mutation in human PMP22, leading to the peripheral neuropathy Dejerine-Sottas syndrome. We have p...

Повний опис

Бібліографічні деталі
Автори: Isaacs, A, Jeans, A, Oliver, P, Vizor, L, Brown, S, Hunter, A, Davies, K
Формат: Journal article
Мова:English
Опубліковано: 2002
_version_ 1826260160179339264
author Isaacs, A
Jeans, A
Oliver, P
Vizor, L
Brown, S
Hunter, A
Davies, K
author_facet Isaacs, A
Jeans, A
Oliver, P
Vizor, L
Brown, S
Hunter, A
Davies, K
author_sort Isaacs, A
collection OXFORD
description We have identified and characterized a new peripheral myelin protein 22 (Pmp22) mouse mutant. The mutation results in a serine to threonine amino acid substitution at residue 72, which is a hot spot for mutation in human PMP22, leading to the peripheral neuropathy Dejerine-Sottas syndrome. We have previously described two other Pmp22 mutants, providing an allelic series for gene function analysis. Pmp22 mutations generally lead to abnormal intracellular trafficking of Pmp22, and we show that each mutant protein in the allelic series has a unique pattern of intracellular localization in transfected cell lines. The mutant protein from the less severely affected mutants occurs in large aggregates, while the mutant protein from the most severely affected mutant occurs in a diffuse perinuclear pattern that largely colocalizes with wild-type protein. This suggests that large Pmp22 aggregates may be protective in this form of peripheral neuropathy.
first_indexed 2024-03-06T19:01:14Z
format Journal article
id oxford-uuid:139733d4-7c33-4c94-b867-8f3b85ee3ee5
institution University of Oxford
language English
last_indexed 2024-03-06T19:01:14Z
publishDate 2002
record_format dspace
spelling oxford-uuid:139733d4-7c33-4c94-b867-8f3b85ee3ee52022-03-26T10:14:46ZIdentification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:139733d4-7c33-4c94-b867-8f3b85ee3ee5EnglishSymplectic Elements at Oxford2002Isaacs, AJeans, AOliver, PVizor, LBrown, SHunter, ADavies, KWe have identified and characterized a new peripheral myelin protein 22 (Pmp22) mouse mutant. The mutation results in a serine to threonine amino acid substitution at residue 72, which is a hot spot for mutation in human PMP22, leading to the peripheral neuropathy Dejerine-Sottas syndrome. We have previously described two other Pmp22 mutants, providing an allelic series for gene function analysis. Pmp22 mutations generally lead to abnormal intracellular trafficking of Pmp22, and we show that each mutant protein in the allelic series has a unique pattern of intracellular localization in transfected cell lines. The mutant protein from the less severely affected mutants occurs in large aggregates, while the mutant protein from the most severely affected mutant occurs in a diffuse perinuclear pattern that largely colocalizes with wild-type protein. This suggests that large Pmp22 aggregates may be protective in this form of peripheral neuropathy.
spellingShingle Isaacs, A
Jeans, A
Oliver, P
Vizor, L
Brown, S
Hunter, A
Davies, K
Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.
title Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.
title_full Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.
title_fullStr Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.
title_full_unstemmed Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.
title_short Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.
title_sort identification of a new pmp22 mouse mutant and trafficking analysis of a pmp22 allelic series suggesting that protein aggregates may be protective in pmp22 associated peripheral neuropathy
work_keys_str_mv AT isaacsa identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy
AT jeansa identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy
AT oliverp identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy
AT vizorl identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy
AT browns identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy
AT huntera identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy
AT daviesk identificationofanewpmp22mousemutantandtraffickinganalysisofapmp22allelicseriessuggestingthatproteinaggregatesmaybeprotectiveinpmp22associatedperipheralneuropathy