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Modeling human RNA spliceosome mutations in the mouse: Not all mice were created equal
Xu, Jane Jialu Smeets, Monique F. Tan, Shuh Ying Wall, Meaghan Purton, Louise E. Walkley, Carl R.
Xu, Jane Jialu
Smeets, Monique F.
Tan, Shuh Ying
Wall, Meaghan
Purton, Louise E.
Walkley, Carl R.
Abstract
Myelodysplastic syndromes (MDS) and related myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are clonal stem cell disorders, primarily affecting patients over 65 years of age. Mapping of the MDS and MDS/MPN genome identified recurrent heterozygous mutations in the RNA splicing machinery, with the SF3B1, SRSF2, and U2AF1 genes being frequently mutated. To better understand how spliceosomal mutations contribute to MDS pathogenesis in vivo, numerous groups have sought to establish conditional murine models of SF3B1, SRSF2, and U2AF1 mutations. The high degree of conservation of hematopoiesis between mice and human and the well-established phenotyping and genetic modification approaches make murine models an effective tool with which to study how a gene mutation contributes to disease pathogenesis. The murine models of spliceosomal mutations described to date recapitulate human MDS or MDS/MPN to varying extents. Reasons for the differences in phenotypes reported between alleles of the same mutation are varied, but the nature of the genetic modification itself and subsequent analysis methods are important to consider. In this review, we summarize recently reported murine models of SF3B1, SRSF2, and U2AF1 mutations, with a particular focus on the genetically engineered modifications underlying the models and the experimental approaches applied.
Keywords
mouse model, spliceosome, myelodysplastic syndrome, myeloproliferative disease, RNA splicing
Date
2019
Type
Journal article
Journal
Experimental Hematology
Book
Volume
70
Issue
Page Range
10-23
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as green open access
License
File Access
Controlled
Open
Open