title: Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.
abstract: 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.
authors.affiliation: Greehey Children's Cancer Research Institute, Department of Cellular and Structural Biology, and.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX;
authors.forename: Marsha C
authors.initials: MC
authors.lastname: Kinney
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia;
authors.forename: Linda M
authors.initials: LM
authors.lastname: Scott
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; and.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Zinkel
authors.affiliation: Greehey Children's Cancer Research Institute, Department of Cellular and Structural Biology, and Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX.
authors.forename: Vivienne I
authors.initials: VI
authors.lastname: Rebel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005818:Genetic Engineering; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*