An increasing number of animal models have been developed for the use of diagnosis, new treatment strategies and advances in supportive care which may contribute to survival rate of the patients with AML. Creative Animodel has inspired by this and has done a lot of work of relevant animal models generation for the use in the discovery of new targets and the testing of new therapies.
Figure 1: Progression to AML (Events: 1. BCR/ABL, AML1/ETO, or Jun-b, etc.; 2. Anti-senescence such as TERT; 3. Anti-apoptosis; 4. Apoptosis receptor pathway silenced; 5. Evade immune cells; 6. Activate and over express self-renewal path genes.)
Chemically induced models:
To perform these models, animals are induced by carcinogenic chemicals and then followed by the leukemia development. The common used models are P388 and L1210 which are induced by 3-Methylcholantrene (3-MC) and intraperitoneally injected into DBA/2 mice. These models can be applied for the discovery of 1-β-D-arabinofuranosylcytosin (cytrabine or Ara-C) in AML treatment.
A spontaneous leukemia can be generated by infecting an oncogenic RNA virus in AKR mice. This model is utilized for the discovery of several drugs including including cyclophosphamide, Ara-C, daunomycin, 5-uorouracil, vincristine, and methotrexate.
Viral models are induced by Murine Leukemia Virus (MuLV) via insertional mutagenesis. At the same time, BXH-2 mice can serve as ecipient mice to express high level of MuLV. BALB/c mice can also induce AML via MuLV injection.
Immunodeficiency mice are most commonly used xenograft models including nude strains, SCID strains, NOD strains, NOD/SCID strains and NSG strains. For more details about these immunodeficiency mice strains in Creative Animodel, please see immunodeficiency mice.
Genetically engineered models (GEMs)
● Transgenic models: PML/RARα, PLZF/RARα and NPM/RARα mouse models are engineered by expressing of RARα fusion protein encoded by promyelocytic leukemia gene (PML). Target gene is carried by a vector which is introduced by electroporation into embryonic stem cells, then transgenic animals can be generated by microinjection. To learn more about animal model creation services, please see Model Creation.
● Knock-in models: This model is generated by targeted insertion of the transgene into a specific locus on the target genome. Our common genetic loci to knock-in fusion genes for developing AML includes AML1-ETO, PLZF-RARα, CBFβ-MYH11 and CBFβ-GFP.
● Knock-out models: AML models with deletion of tumor suppressors (i.e. PTEN and NF1) are generated by using LoxP/Cre systems.
Besides mice, Creative Animodel has also developed rat and zebrafish as models to study AML according to different needs. To learn more about customized models, please feel free to contact us.