Sandra Zinkel
Assistant Professor of Medicine
Last active: 3/26/2019

Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.

Zhou T, Kinney MC, Scott LM, Zinkel SS, Rebel VI
Blood. 2015 126 (9): 1057-68

PMID: 26077396 · PMCID: PMC4551359 · DOI:10.1182/blood-2015-01-624239

Much-needed attention has been given of late to diseases specifically associated with an expanding elderly population. Myelodysplastic syndrome (MDS), a hematopoietic stem cell-based blood disease, is one of these. The lack of clear understanding of the molecular mechanisms underlying the pathogenesis of this disease has hampered the development of efficacious therapies, especially in the presence of comorbidities. Mouse models could potentially provide new insights into this disease, although primary human MDS cells grow poorly in xenografted mice. This makes genetically engineered murine models a more attractive proposition, although this approach is not without complications. In particular, it is unclear if or how myelodysplasia (abnormal blood cell morphology), a key MDS feature in humans, presents in murine cells. Here, we evaluate the histopathologic features of wild-type mice and 23 mouse models with verified myelodysplasia. We find that certain features indicative of myelodysplasia in humans, such as Howell-Jolly bodies and low neutrophilic granularity, are commonplace in healthy mice, whereas other features are similarly abnormal in humans and mice. Quantitative hematopoietic parameters, such as blood cell counts, are required to distinguish between MDS and related diseases. We provide data that mouse models of MDS can be genetically engineered and faithfully recapitulate human disease.

© 2015 by The American Society of Hematology.

MeSH Terms (8)

Animals Disease Models, Animal Genetic Engineering Hematopoiesis Hematopoietic Stem Cells Humans Mice Myelodysplastic Syndromes

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