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• W3033702012 abstract "Loss-of-Function (LOF) of the potassium chloride cotransporter 3 (KCC3) results in hereditary sensorimotor neuropathy with Agenesis of the Corpus Callosum (HSMN/ACC). Our KCC3 knockout mouse recapitulated axonal swelling and tissue vacuolization observed in autopsies of individuals with HSMN/ACC. We previously documented the first human case of a KCC3 gain-of-function (GOF) in which the patient also exhibited severe peripheral neuropathy. Furthermore, the GOF mouse model exhibited shrunken axons implicating the cotransporter in cell volume homeostasis. It is unclear how both KCC3 LOF and GOF lead to peripheral neuropathy. Thus, we sought to study differences in cell volume regulation of dorsal root ganglion neurons isolated from different mouse lines.Using wide-field microscopy, we measured calcein fluorescence intensity through pinhole measurements at the center of cells and compared cell swelling and cell volume regulation/recovery of wild-type, LOF, and GOF dorsal root ganglia neurons, as well as wild-type neurons treated with a KCC-specific inhibitor.In contrast to control neurons that swell and volume regulate under a hypotonic challenge, neurons lacking KCC3 swell but fail to volume regulate. Similar data were observed in wild-type neurons treated with the KCC inhibitor. We also show that sensory neurons expressing a constitutively active KCC3 exhibited a blunted swelling phase compared to wild-type neurons, questioning the purely osmotic nature of the swelling phase.These findings demonstrate the integral role of KCC3 in cell volume homeostasis and support the idea that cell volume homeostasis is critical to the health of peripheral nerves." @default.
• W3033702012 created "2020-06-12" @default.
• W3033702012 creator A5088649225 @default.
• W3033702012 creator A5091542226 @default.
• W3033702012 date "2020-06-08" @default.
• W3033702012 modified "2023-09-27" @default.
• W3033702012 title "Osmotic Response of Dorsal Root Ganglion Neurons Expressing Wild-Type and Mutant KCC3 Transporters" @default.
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• W3033702012 doi "https://doi.org/10.33594/000000241" @default.
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