Animal Models of Myeloproliferative Neoplasms
Animal models have been widely used for myeloproliferative neoplasms (MPNs) researches and also have played a vital role in advancing MPNs biology and therapy. To facilitate the preclinical studies of MPNs, Creative Animodel has addressed a board range of models including retroviral, genetically engineered and xenograft models to better recapitulate human diseases in animals especially in mice. These models have provided an outstanding platform to characterize the abnormalities of MPNs and to test novel MPNs therapeutic agents.
To create this model, we transduce BCR-ABL into murine bone marrow and then transplant bone marrow cells into irradiated syngeneic mice. Combined with bone marrow transplantation assay, this model is able to reproduce human hematologic malignancies in mice.
● Retroviral models: The retroviral BCR-ABL model gives new insights into the molecular pathophysiology of MPNs in human including the effect of BCR-ABL expression in vivo to induce MPNs, the signaling pathways of BCR-ABL in stem cells and the evaluation of novel approaches for MPNs therapy.
● Transgenic models: We have generated two types of transgenic mice to investigate the molecular pathogenesis of MPNs: mice expressing Sca-1 driven BCR-ABL and double transgenic SCLtTA/BCR-ABL mice.
● Xenograft models: This model is created by transplanting BCR-ABL positive cells which are selected from long-term culture-initiating cell (LT-CIC) into SCID mice.
Single point of mutation in the JAK2 kinase has been found in the patient with MPNs, which has bought considerable studies in the mechanism of JAK2V617F mutation in the hematopoietic system.
● Bone marrow transplantation models: Expression of JAK2V617F has been certified by several studies of bone marrow transplantation as a sufficiency to induce an MPN-like phenotype in mice. Thus, we use retroviruses to overexpress JAK2V617F in bone barrow cells and then transplant these cells into mice to generate a model. The recipient can be BALB/c or C57BL/6.
● Transgenic models: Pronuclear injection is used to generate transgenic lines of mice with JAK2V617F expression.
● Knock-in models: We have successfully generated conditional JAK2V617F knock-in model to recapitulate human MPNs through physiological JAK2V617F expression.
Figure: Genetic strategies for generating mouse models of JAK2V617F-positive MPNs.
Genetic lesions which have been described in the epigenetic machinery in MPNs such as in MPLW515L, TET2, LNK and c-CBL mutation can also be developed to present genetic abnormalities. Creative Animodel has rich experience in animal model creation, and is able to expand our services to study the molecular consequences of diseases by using most advanced genome-editing technologies and traditional model creation approaches. We aim to be the world class animal models supplier and to provide valuable disease models for therapeutic studies. To learn more about our customized model creation services, please feel free to contact us.