The potassium chloride cotransporter, KCC3, is an electroneutral cotransporter expressed in the peripheral and central nervous system. KCC3 is responsible for the efflux of K+ and Cl- in neurons to help maintain cell volume and intracellular chloride levels. A loss-of-function (LOF) of KCC3 causes Hereditary Motor Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) in a population of individuals in the Charlevoix/Lac-Saint-Jean region of Quebec, Canada. A variety of mouse models have been created to understand the physiological and deleterious effects of a KCC3 LOF. Though this KCC3 LOF in mouse models has recapitulated the peripheral neuropathy phenotype of HMSN/ACC, we still know little about the development of the disease pathophysiology. Interestingly, the most recent KCC3 mouse model that we created recapitulated a peripheral neuropathy-like phenotype originating from a KCC3 gain-of-function (GOF). Despite the past two decades of research in attempting to understand the role of KCC3 in disease, we still do not understand how dysfunction of this cotransporter can lead to the pathophysiology of peripheral neuropathy. This review focuses on the function of KCC3 in neurons and its role in human and health and disease.

中文翻译：

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KCC3 在维持周围神经纤维细胞体积中的作用。

氯化钾协同转运蛋白 KCC3 是一种在外周和中枢神经系统中表达的电中性协同转运蛋白。KCC3 负责神经元中 K+ 和 Cl- 的流出，以帮助维持细胞体积和细胞内氯化物水平。KCC3 的功能丧失 (LOF) 导致加拿大魁北克省 Charlevoix/Lac-Saint-Jean 地区的人群中的遗传性运动感觉神经病伴胼胝体发育不全 (HMSN/ACC)。已经创建了多种小鼠模型来了解 KCC3 LOF 的生理和有害影响。尽管小鼠模型中的这种 KCC3 LOF 概括了 HMSN/ACC 的周围神经病变表型，但我们对疾病病理生理学的发展仍然知之甚少。有趣的是，我们创建的最新 KCC3 小鼠模型概括了源自 KCC3 功能获得 (GOF) 的周围神经病变样表型。尽管过去二十年的研究试图了解 KCC3 在疾病中的作用，但我们仍然不了解这种协同转运蛋白的功能障碍如何导致周围神经病变的病理生理学。本综述侧重于 KCC3 在神经元中的功能及其在人类、健康和疾病中的作用。