Friday, August 21, 2015

Studies in fly and mouse help elucidate causes and possible therapeutic for erythrokeratodermia variabilis

Tang C, Chen X, Chi J, Yang D, Liu S, Liu M, Pan Q, Fan J, Wang D, Zhang Z. Pathogenic Cx31 Is Un/misfolded to Cause Skin Abnormality via A Fos/JunB-Mediated Mechanism. Hum Mol Genet. 2015 Aug 6. PMID: 26251042.

From the abstract: "Mutations in connexin-31 (Cx31) are associated with multiple human diseases, including familial erythrokeratodermia variabilis (EKV). The pathogenic mechanism of EKV associated Cx31 mutants remains largely elusive. Here, we show that EKV pathogenic Cx31 mutants are un/misfolded and temperature sensitive. In Drosophila, expression of pathogenic Cx31, but not wildtype Cx31, causes depigmentation and degeneration of ommatidia that are rescued by expression of either dBip or dHsp70. Ectopic expression of Cx31 in mouse skin results in skin abnormalities resembling human EKV. The affected tissues show remarkable disrupted gap junction formation and significant upregulation of chaperones Bip and Hsp70 as well as AP-1 proteins c-Fos and JunB, in addition to molecular signatures of skin diseases. ..."

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