001047356 001__ 1047356
001047356 005__ 20251030202116.0
001047356 0247_ $$2doi$$a10.1038/s41598-025-19757-2
001047356 0247_ $$2datacite_doi$$a10.34734/FZJ-2025-04252
001047356 037__ $$aFZJ-2025-04252
001047356 082__ $$a600
001047356 1001_ $$0P:(DE-Juel1)176837$$aBalduin, Carina$$b0$$ufzj
001047356 245__ $$aDisruption of ClC-3-mediated 2Cl−/H+ exchange leads to behavioural deficits and thalamic atrophy
001047356 260__ $$a[London]$$bSpringer Nature$$c2025
001047356 3367_ $$2DRIVER$$aarticle
001047356 3367_ $$2DataCite$$aOutput Types/Journal article
001047356 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1761827758_23646
001047356 3367_ $$2BibTeX$$aARTICLE
001047356 3367_ $$2ORCID$$aJOURNAL_ARTICLE
001047356 3367_ $$00$$2EndNote$$aJournal Article
001047356 500__ $$aOpen Access funding enabled and organized by Projekt DEAL.
001047356 520__ $$aCLCN3 encodes ClC-3, an endosomal 2Cl⁻/H⁺ exchanger, with pathogenic variants causing aneurodevelopmental condition marked by developmental delays, intellectual disability, seizures,hyperactivity, anxiety, and brain and retinal abnormalities. Clcn3−/− mice show hippocampal and retinaldegeneration, recapitulating key symptoms observed in humans. ClC-3 forms homodimers (ClC-3/ClC-3) and heterodimers with ClC-4 (ClC-3/ClC-4), with overlapping brain expression. This suggestsdistinct functional roles for homo- and heterodimeric assemblies and raises the question of which brainregions specifically depend on ClC-3/ClC-3 rather than ClC-3/ClC-4 complexes. Using ex vivo PET traceranalyses, Clcn3−/− and Clcn3td/td mice, we found neurodegeneration in the hippocampus and thalamusof Clcn3−/−, while Clcn3td/td mice showed thalamic degeneration and altered neuronal excitability,including changes in action potential threshold and after hyperpolarization. Clcn3td/td mice carryinga transport-deficient p.E281Q ClC-3 variant that still associates with ClC-4, thereby allowing ClC-4 tobe sorted to endosomes as ClC-4/ClC-3 heterodimers, unlike in the Clcn3−/− model. Clcn3td/td mice alsoexhibited reduced weight, hyperactivity, and motor deficits, reflecting clinical features. Lower ClC-4levels in thalamus predict a predominant thalamic expression of ClC-3/ClC-3 homodimers. Overall,our findings indicate a region-specific function of ClC-3/ClC-3 homodimeric complexes and highlightthe importance of ClC-3 transport activity in thalamic neuron survival, with electrophysiologicaldysfunction likely contributing to neurodegeneration.
001047356 536__ $$0G:(DE-HGF)POF4-5241$$a5241 - Molecular Information Processing in Cellular Systems (POF4-524)$$cPOF4-524$$fPOF IV$$x0
001047356 536__ $$0G:(DE-HGF)POF4-5253$$a5253 - Neuroimaging (POF4-525)$$cPOF4-525$$fPOF IV$$x1
001047356 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de
001047356 7001_ $$0P:(DE-Juel1)131702$$aQi, Guanxiao$$b1$$ufzj
001047356 7001_ $$0P:(DE-Juel1)131792$$aSchöneck, Michael$$b2$$ufzj
001047356 7001_ $$0P:(DE-Juel1)169937$$aTrinkel, Verena$$b3
001047356 7001_ $$0P:(DE-Juel1)165908$$aSchemmert, Sarah$$b4$$ufzj
001047356 7001_ $$0P:(DE-Juel1)165956$$aGuzman, Gustavo A.$$b5
001047356 7001_ $$0P:(DE-HGF)0$$aBungert-Plümke, Stefanie$$b6
001047356 7001_ $$0P:(DE-HGF)0$$aKlüssendorf, Malte$$b7
001047356 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b8$$ufzj
001047356 7001_ $$0P:(DE-Juel1)131680$$aFeldmeyer, Dirk$$b9$$ufzj
001047356 7001_ $$0P:(DE-Juel1)131794$$aShah, N. Jon$$b10$$ufzj
001047356 7001_ $$0P:(DE-HGF)0$$aStauber, Tobias$$b11
001047356 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b12$$ufzj
001047356 7001_ $$0P:(DE-Juel1)156375$$aGuzman, Raul E.$$b13$$eCorresponding author$$ufzj
001047356 7001_ $$0P:(DE-Juel1)144347$$aWilluweit, Antje$$b14$$eCorresponding author$$ufzj
001047356 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-025-19757-2$$gVol. 15, no. 1, p. 33326$$n1$$p33326$$tScientific reports$$v15$$x2045-2322$$y2025
001047356 8564_ $$uhttps://juser.fz-juelich.de/record/1047356/files/Scientific_Reports_Bungert_Guzman_09_2025.pdf$$yOpenAccess
001047356 909CO $$ooai:juser.fz-juelich.de:1047356$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)176837$$aForschungszentrum Jülich$$b0$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131702$$aForschungszentrum Jülich$$b1$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131792$$aForschungszentrum Jülich$$b2$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)165908$$aForschungszentrum Jülich$$b4$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-HGF)0$$aForschungszentrum Jülich$$b6$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)166419$$aForschungszentrum Jülich$$b8$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131680$$aForschungszentrum Jülich$$b9$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131794$$aForschungszentrum Jülich$$b10$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131777$$aForschungszentrum Jülich$$b12$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)156375$$aForschungszentrum Jülich$$b13$$kFZJ
001047356 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)144347$$aForschungszentrum Jülich$$b14$$kFZJ
001047356 9131_ $$0G:(DE-HGF)POF4-524$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5241$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vMolecular and Cellular Information Processing$$x0
001047356 9131_ $$0G:(DE-HGF)POF4-525$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5253$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vDecoding Brain Organization and Dysfunction$$x1
001047356 9141_ $$y2025
001047356 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSCI REP-UK : 2022$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-07-29T15:28:26Z
001047356 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-07-29T15:28:26Z
001047356 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
001047356 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2024-12-18
001047356 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-18
001047356 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
001047356 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-18
001047356 920__ $$lyes
001047356 9201_ $$0I:(DE-Juel1)IBI-1-20200312$$kIBI-1$$lMolekular- und Zellphysiologie$$x0
001047356 9201_ $$0I:(DE-Juel1)ETN-20090406$$kETN$$lProjektträger Energie, Technologie, Nachhaltigkeit$$x1
001047356 9201_ $$0I:(DE-Juel1)INM-10-20170113$$kINM-10$$lJara-Institut Brain structure-function relationships$$x2
001047356 9201_ $$0I:(DE-Juel1)INM-4-20090406$$kINM-4$$lPhysik der Medizinischen Bildgebung$$x3
001047356 9201_ $$0I:(DE-Juel1)IBI-7-20200312$$kIBI-7$$lStrukturbiochemie$$x4
001047356 9201_ $$0I:(DE-Juel1)INM-5-20090406$$kINM-5$$lNuklearchemie$$x5
001047356 980__ $$ajournal
001047356 980__ $$aVDB
001047356 980__ $$aUNRESTRICTED
001047356 980__ $$aI:(DE-Juel1)IBI-1-20200312
001047356 980__ $$aI:(DE-Juel1)ETN-20090406
001047356 980__ $$aI:(DE-Juel1)INM-10-20170113
001047356 980__ $$aI:(DE-Juel1)INM-4-20090406
001047356 980__ $$aI:(DE-Juel1)IBI-7-20200312
001047356 980__ $$aI:(DE-Juel1)INM-5-20090406
001047356 9801_ $$aFullTexts