Atp2c1-KO Mouse

ATP2C1, encoding the secretory pathway Ca(2+)/Mn(2+)-ATPase pump type 1 (SPCA1) [2], functions to maintain normal intracellular concentrations of Ca2+/Mn2+ by transporting them into the Golgi apparatus [1]. This process is crucial for normal cellular function, potentially affecting multiple cellular pathways related to cell adhesion and differentiation [1,2,4,7,10].

Mutations in ATP2C1 have been identified as the cause of Hailey-Hailey disease (HHD), a rare autosomal dominant acantholytic dermatosis [1,2,3,4,5,6,7,8,9,10]. Loss of ATP2C1 function promotes trafficking and degradation of NOTCH1, likely contributing to HHD manifestation as Notch signalling is a determinant of keratinocyte growth and differentiation [4]. Also, ATP2C1 knockdown in keratinocytes leads to abnormal expressions of cytoskeletal and tight junction proteins, mimicking the acantholysis seen in HHD [10].

In conclusion, ATP2C1 is essential for maintaining proper intracellular Ca2+/Mn2+ levels, which is crucial for normal cell function. Studies, especially those using loss-of-function models like ATP2C1 knockdown in keratinocytes, have revealed its significant role in the pathogenesis of HHD, highlighting its importance in understanding and potentially treating this skin disorder [1,2,4,10].