Loss of MPZL3 Function Causes Seborrheic Dermatitis-like Phenotype in Mice

Seborrheic Dermatitis (SD) is a common inflammatory skin disorder. In this study, we demonstrated SD-like clinical features with associated histology in the Mpzl3 knockout(-/-) mice. Mpzl3-/- skin showed increased macrophage and CD4+ lymphocyte infiltration, however adaptive immunity was not required for the onset of skin inflammation. Furthermore, we detected epidermal barrier defects as suggested by increased dye permeability in Mpzl3-/- embryos and altered gene expression by microarray analysis in pup skin. Taken together, these findings suggest MPZL3 plays an essential role in epidermal differentiation and barrier function, and underscore the interplay between epidermal barrier and immunity in SD. The SD-like clinical and histologic features in the Mpzl3-/- mice also resemble those in patients carrying a frame-shift mutation in ZNF750, a key regulator of epidermal differentiation and a transcriptional activator of the MPZL3 gene. Therefore, we conclude that the ZNF750/MPZL3 pathway plays a critical role in the pathogenesis of SD, and a better understanding of skin inflammation and barrier restoration in the Mpzl3-/- mice will provide insight into the pathogenesis and treatment/prevention of recurrent SD. Comparison of gene expression of Mpzl3 -/- and +/+ mouse skin: Total RNA was extracted from the dorsal skin of mouse pups with TriZol Reagent (Life Technologies, Grand Island, NY) and purified with the RNeasy mini kit (Qiagen, Germantown, MD). RNA was sent to the John P. Hussman Institute for Human Genomics Gene Expression Core Facility at the University of Miami Miller School of Medicine for microarray analysis using the Agilent Whole Mouse Genome (4x44K) array from Agilent (Santa Clara, CA).