• Modeling Mechanism：

  Tamoxifen activates the AP-1 transcription factor (upregulating the expression of c-fos, c-jun, and ap1s1 by 3-7 times), driving the potent expression of MMP family genes (especially mmp9 and mmp13a) in skin epithelial cells (upregulated by 127-fold and 1145-fold, respectively). Excessive MMPs degrade the extracellular matrix, inducing skin epithelial cell cytotoxicity, apoptosis, and necrosis, ultimately leading to the tail necrosis phenotype.

• Related Products：

  Tamoxifen (T6906)

• Modeling Method：

  Experimental Subject：

  Zebrafish: Wild-type tropical 5D strain, secA5-YFP transgenic strain (visualisation of apoptosis). Embryonic stage (4–5 hpf post-eclosion), juvenile stage (48 hpf) to adult.

  Dosage and Administration Route：

  1–15 μM tamoxifen (dissolved in 0.1% DMSO, final concentration) Static exposure in embryo medium Exposure by placing embryos/larvae individually in 96-well plates (containing 100 μL embryo medium); adult fish exposed directly to drug-containing medium

  Dosing Frequency and Duration Model：

  Embryonic stage: Continuous exposure from 6–120 hpf; Larval stage: Single 24-hour exposure at 48–72 hpf; Adult stage: Single 1.5-hour exposure

• Validation：

  Phenotypic validation: Specific necrosis appeared in the tail, which could extend to the pectoral fins and the entire skin of adult fish. Apoptotic signals (secA5-YFP) were spatiotemporally colocalized with the necrotic area. Molecular markers: qRT-PCR showed significant upregulation of genes such as mmp9, mmp13a, and igfbp1a. Immunohistochemistry confirmed high expression of MMP13a protein in the tail injury area. Specificity validation: Knockdown of ER inhibitors (G-15), p53 inhibitors (pifithrin α), and ER (esr1, esr2a, esr2b) morpholino did not improve the phenotype, while MMP inhibitors (EDTA, GM 6001, SR 11302) could completely or partially block the necrotic phenotype. Dose-relatedness: 1-5 μM had no obvious phenotype, ≥10 μM induced 100% tail necrosis, and 15 μM was accompanied by increased mortality.

*Precautions：

*References：Bugel SM,et,al. Phenotype anchoring in zebrafish reveals a potential role for matrix metalloproteinases (MMPs) in tamoxifen's effects on skin epithelium. Toxicol Appl Pharmacol. 2016 Apr 1;296:31-41.