Disease relevance of Clcn7

• Mutations in ClC-7, a late endosomal/lysosomal member of the CLC family of chloride channels and transporters, cause osteopetrosis and lysosomal storage disease in humans and mice [1].
• ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function [1].

High impact information on Clcn7

• Mutation of one Clcn7 M-box prevented MITF transactivation, but mutation of the second MITF-binding site only reduced basal activity [2].
• The Clcn7 promoter was transactivated by coexpression of MITF in reporter gene assays [2].
• However, the expression and functional role of Cl- transporters other than ClC7 in mammalian osteoclasts is unknown [3].
• INTRODUCTION: Mice with deficient chloride (Cl-) channels, ClC7, show severe osteopetrosis, resulting from impairment of Cl- extrusion during osteoclastic bone resorption [3].
• ClC-7 is required for Ostm1 to reach lysosomes, where the highly glycosylated Ostm1 luminal domain is cleaved [1].

Anatomical context of Clcn7

• Here we show that both ClC-7 and Ostm1 proteins co-localize in late endosomes and lysosomes of various tissues, as well as in the ruffled border of bone-resorbing osteoclasts [1].

Analytical, diagnostic and therapeutic context of Clcn7

• Chromatin immunoprecipitation assays confirmed that the two Clcn7 MITF binding and responsive regions in vitro bind MITF in genomic DNA [2].
• Using electrophoretic mobility shift assays, we identified two MITF-binding sites (M-boxes) in the Clcn7 promoter and a single M-box in the Ostm1 promoter [2].

References