Anti Zebrafish tp53 antibody (ZABALA1)

TP53 Research in Zebrafish Models

Zebrafish (Danio rerio) serve as a valuable model organism for studying the TP53 gene due to its high structural and functional similarity to mammalian p53. Zebrafish embryos are transparent and develop externally, making them ideal for observing early developmental processes and disease mechanisms in vivo.

Key areas of TP53 research utilizing zebrafish include:

• Tumor Suppression: Zebrafish models with compromised tp53 function (e.g., tp53 null or mutant alleles) spontaneously develop various tumors, including malignant peripheral nerve sheath tumors (MPNSTs), angiosarcomas, germ cell tumors, and aggressive NK-cell-like leukemia, highlighting its conserved tumor suppressor role. Studies show that tp53 is a major suppressor of tumor initiation, particularly in RAS-driven embryonal rhabdomyosarcoma (ERMS), where its loss significantly increases tumor incidence and growth.

• Li-Fraumeni Syndrome (LFS) Modeling: Zebrafish with specific tp53 hotspot mutations (e.g., tp53 R217H and R242H, orthologous to human R248H and R273H) recapitulate key LFS phenotypes, including dysfunctional p53 hallmarks (defective cell-cycle checkpoints, resistance to apoptosis) and spontaneous tumor development resembling human sarcomas. These models provide insights into tumorigenesis mechanisms and potential therapeutic targets for LFS.

• Apoptosis and Stress Response: Zebrafish p53 is a crucial mediator of apoptosis in response to various stimuli, including DNA damage (e.g., UV irradiation, topoisomerase inhibitors). Studies demonstrate that p53 knockdown or mutation in zebrafish embryos leads to a decreased induction of apoptosis upon DNA-damaging stimuli.

• Developmental Roles: Beyond its tumor suppressor function, p53 in zebrafish is involved in regulating brain development via stress signals and promoting cardiomyocyte proliferation and heart regeneration.

• Pathway Conservation: The p53 regulatory pathway, including negative feedback loops with MDM2, is evolutionarily conserved in zebrafish, providing a robust system for uncovering novel modifier genes and therapeutic agents for human diseases.

• Drug Discovery: Zebrafish models with tp53 mutations offer a platform for high-throughput screens to identify genetic mutations or small molecules that affect tp53-related pathways, such as those involved in apoptosis and cell cycle.

Research in zebrafish has contributed significantly to understanding the complex functions of TP53 in development, stress response, and cancer, further solidifying its importance as a model for human disease.