Loss of MPZL3 function causes seborrhoeic dermatitis‐like phenotype in mice

Increased IL‐17‐expressing γδ T cells in seborrhoeic dermatitis‐like lesions of the Mpzl3 knockout mice

“…Importantly, S100a8 and S100a9, markers for damage‐associated molecular patterns, were significantly up‐regulated in Mpzl3 −/− lesional skin compared with control (Figure C). These observations are consistent with our previous results showing perturbed epidermal differentiation gene expression pattern and consequently epidermal barrier defects . Furthermore, these results suggest an up‐regulation of pro‐inflammatory cytokines in the early onset of skin inflammation in response to structural defects in the Mpzl3 −/− skin.…”

“…Within 3 weeks after birth, skin inflammation becomes apparent in the muzzle areas and around the eyes of the Mpzl3 knockout (−/−) mice (Figure A) . At 22 days after birth, real‐time qPCR detected increased steady‐state mRNA expression of keratinocyte differentiation markers keratin 1, filaggrin, involucrin and Sprr2a in Mpzl3 −/− lesional skin compared with skin from corresponding areas of sex‐matched +/+ littermates (N = 5 each) (Figure C), verifying the epidermal hyperplasia of lesional skin observed in histology (Figure B) . Additionally, significant increases were detected in various pro‐inflammatory cytokine mRNA levels, such as IL‐1α, IL‐1β and IL‐17a, in the Mpzl3 −/− lesional skin (Figure C).…”

“…Both SD and dandruff are chronic and relapsing, but their pathophysiology is poorly understood. The inherited SD caused by ZNF750 mutation in patients and Mpzl3 gene knockout in mice suggests that the ZNF750/MPZL3 pathway plays a critical role in SD pathogenesis, and underscores the role of abnormal epidermal differentiation in SD pathogenesis . Both ZNF750 and MPZL3 are key regulators of keratinocyte terminal differentiation .…”

“…This observation underscores the role of epidermal differentiation in SD aetiology. Importantly, we have previously shown that knockout mice of the Mpzl3 (Myelin Protein Zero‐like 3, OMIM #611707) gene, a direct downstream target of ZNF750, develop SD‐like phenotype . These observations make the Mpzl3 knockout (−/−) mice a suitable model to study mechanisms of SD pathophysiology.…”

The Association Between Polycystic Ovary Syndrome and Its Dermatological Manifestations

“…Several studies have been conducted to uncover the profundity of its molecular mechanisms. In one study, a great number of immune cells were identified, such as interleukin-17 (IL-17), CD45+ leukocytes, CD5+ lymphocytes, γⴃT cells in connection to it and ZNF750/MPZL3 pathway, which plays a critical part in the pathogenesis of SD [23,24]. Additionally, this inflammatory aggregation in SD disrupts the skin barrier called the epidermis and further produces an immune reaction to Malassezia yeasts [25].…”