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Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1

Item Type:Article
Title:Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1
Creators Name:Pressey, S.N. and O'Donnell, K.J. and Stauber, T. and Fuhrmann, J.C. and Tyynelae, J. and Jentsch, T.J. and Cooper, J.D.
Abstract:The proteins ClC-6 and ClC-7 are expressed in the endosomal-lysosomal system. Because Clcn6-deficient mice display some features of neuronal ceroid lipofuscinosis (NCL), CLCN6 may be a candidate gene for novel forms of NCL. Using landmarks of disease progression from NCL mouse models as a guide, we examined neuropathologic alterations in the central nervous system of Clcn6, Clcn7, andgl mice. gl mice bear a mutation in Ostm1, the beta-subunit critical for Clcn7 function. Severely affected Clcn7 and gl mice have remarkably similar neuropathologic phenotypes, with pronounced reactive changes and neuron loss in the thalamocortical system, similar to findings in early-onset forms of NCL. In contrast, Clcn6 mice display slowly progressive, milder neuropathologic features with very little thalamic involvement or microglial activation. These findings detail for the first time the markedly different neuropathologic consequences of mutations in these two CLC genes. Clcn7 and gl mice bear a close resemblance to the progressive neuropathologic phenotypes of early onset forms of NCL, whereas the distinct phenotype of Clcn6-deficient mice suggests that this gene could be a candidate for a later-onset form of mild neurologic dysfunction with some NCL-like features.
Keywords:Chloride Channel, Chloride/Proton Exchanger, Grey Lethal, Lysosomal Storage Disorder, Neuronal Ceroid Lipofuscinosis/Batten Disease, Animals, Mice
Source:Journal of Neuropathology and Experimental Neurology
ISSN:0022-3069
Publisher:Lippincott, Williams & Wilkins (U.S.A.)
Volume:69
Number:12
Page Range:1228-1246
Date:December 2010
Official Publication:https://doi.org/10.1097/NEN.0b013e3181ffe742
PubMed:View item in PubMed

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