Myelodysplastic syndromes (MDS) is a kind of malignancies in hematopoietic system which is characterized by dysplastic bone marrow as a result of mutations in the hematopoietic stem/progenitor cell (HSPC). Due to the heterogeneity of MDS, significant efforts have been made recently to develop appropriate animal models and to study the complex etiology of this disease.Creative Animodel has generated several MDS mice models by gene targeting or viral transduction to capture the MDS phenotype in its entirety, and has made advances in our understanding of mechanisms within the malignant clone and the bone marrow microenvironment.
Approaches to model MDS in mice:
● Treated by mutagens or carcinogens
● Xenotransplantation of human MDS cells
● Genetic engineering of mouse hematopoietic cells
Xenograft models of MDS
● Transgenic severe combined immunodeficient (SCID) mice expressing human growth factors can provide the environment for increased engraftment of immortal cell lines derived from MDS patients.
● Non-obese diabetic (NOD-scid) mice are provided to resolve the obstacle of immune rejection in xenotransplantation assay.
● NOD-scid β2-microglobulin-deficient mice (NOD-scid B2mnull) can help to improve engraftment of MDS precursors.
● NOD-scid IL2Rγnull (NSG) mice present a good immunocompromised hosts for grafts
Available genetically engineered mouse models with relevant genes and techniques of MDS
● Cd74–Nid67 (Likely RPS14): Large-scale chromosomal deletion of syntenic region within 5q CDR
● miR-145 and miR-146a: Retroviral transduction
● Dicer1/sbds: Osterix-Cre-Dicer1fl/fl mice, Osterix-Cre-Sbdsfl/fl mice
● NUP98–HOXD13: Transgenic NUP98–HOXD13 (Vav promoter)
● Runx1: Retroviral transduction (D171N missense mutation or S291fsX300 frameshift mutation)
● Evi1: Retroviral transduction
● Pten/Ship: Pten+/-Ship-/-
● Npm1: Heterozygous hypomorphic Npm1 mutant
● SALL4: Transgenic (CMV promoter)
● BCL2/NRASD12: Transgenic (BCL2-tTA, and NRASD12-MRP8 promoters)
● Arid4a: Knockout
● Polg: Knock-in of Poly D257A missense germline mutation
● Dido: Knockout
● Fbw7-mediated cyclin E degradation: Knockin mice (cyclin ET74A/T393A mutation)
● TGF-B1: Constitutive hepatic expression of TGFB1 (Alb/TGF fusion gene)
● SPARC: Knockout
● EGR1 deficiency: Egr1-knockout mice treated with ENU to induce secondary cooperating mutations
● APCmin (adenomatosis polyposis coli): Mx1-Cre+ Apcfl/+ haploinsufficient mice
Creative Animodel has successfully created MDS animal models with these candidate genes to reveal their influence on disease mechanisms. We have been at the forefront of animal model creation, and are able to ensure your experimental objective can be met on time and in a cost-efficient manner. All of our efforts of making animal models aim to help facilitate the development of new drugs and pre-clinical evaluation of new therapeutic approaches. To learn more about how we can help with your individualized studies, please feel free to contact us.