Establishment of a Mouse Model for Porokeratosis Due to Mevalonate Diphosphate Decarboxylase Deficiency.

INTRODUCTION: Porokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by circular or annular skin lesions with a hyperkeratotic rim, pathologically shown as the cornoid lamella. Four genes that cause PK are associated with the mevalonate (MV) pathway. In Chinese PK patients, mevalonate diphosphate decarboxylase (MVD) is the most common causative gene. The lack of an animal model has greatly limited research on PK pathogenesis. MATERIALS AND METHODS: In this research, we constructed K14-CreERT2-Mvdfl/fl mice using the Cre-LoxP system to create a mouse model for in-depth studies of PK. The Epidermal Mvd gene was knocked out by intraperitoneal injection of Tamoxifen (TAM). Pathology, immunohistochemistry, RNA-seq, and Western Blot analysis were performed. RESULTS: Skin lesions appeared following Mvd deficiency, and pathological examination revealed the characteristic cornoid lamella, as well as cutaneous inflammation. Furthermore, we observed elevated levels of IL-17A and IL-1ß, and a decreased Loricrin level in epidermal Mvd-deficient mice. Compared with the wild-type (WT) group, Mvd deficiency activated the expression of lipid metabolism-related proteins. CONCLUSION: We developed the first mouse model for PK research, enabling further studies on disease development and treatment approaches.

MiT family translocation renal cell carcinoma with retroperitoneal metastasis in childhood: a case report.

RCC accounts for only 0.1%-0.3% of all kidney tumors and 2%-6% of malignant kidney tumors in children. Accounting for approximately one-third of the total number of cases in children and adolescents with RCC, Xp11.2 tRCC is the most common subtype of the MiT family translocation renal cell carcinoma, which is a group of rare childhood and adult tumors, characterized by recurrent gene rearrangements of TFE3. Here we report a rare case of a 6-year-old male patient with MiT family translocation renal cell carcinoma (MiTF tRCC) where the patient developed retroperitoneal metastasis. The patient underwent partial nephrectomy (PN), radical nephrectomy (RN), abdominal lymph node resection, and intestinal adhesion lysis. Microscopically, we detected focal and nest clump-shaped clusters of tumor cells whose cytoplasm was bright and clear. Immunohistochemistry (IHC) showed tumor cells diffusely expressed TFE3, and fluorescence in situ hybridization (FISH) demonstrated disruption of the TFE3 locus, confirming the diagnosis of Xp11.2 tRCC, the most common subtype of MiTF tRCC. Eventually, the patient obtained a good therapeutic result. This case can provide a good reference and guidance for pediatric urologists and oncologists to recognize and diagnose rare renal cell carcinoma in children.