Modeling human RNA spliceosome mutations in the mouse: Not all mice were created equal
Journal article
Xu, Jane Jialu, Smeets, Monique F., Tan, Shuh Ying, Wall, Meaghan, Purton, Louise E. and Walkley, Carl R.. (2019). Modeling human RNA spliceosome mutations in the mouse: Not all mice were created equal. Experimental Hematology. 70, pp. 10 - 23. https://doi.org/10.1016/j.exphem.2018.11.001
Authors | Xu, Jane Jialu, Smeets, Monique F., Tan, Shuh Ying, Wall, Meaghan, Purton, Louise E. and Walkley, Carl R. |
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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 |
Year | 2019 |
Journal | Experimental Hematology |
Journal citation | 70, pp. 10 - 23 |
Publisher | Elsevier Inc. |
ISSN | 0301-472X |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.exphem.2018.11.001 |
Scopus EID | 2-s2.0-85057017717 |
Open access | Published as green open access |
Page range | 10 - 23 |
Research Group | Mary MacKillop Institute for Health Research |
Author's accepted manuscript | License File Access Level Open |
Publisher's version | License All rights reserved File Access Level Controlled |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/881q7/modeling-human-rna-spliceosome-mutations-in-the-mouse-not-all-mice-were-created-equal
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Author's accepted manuscript
AM_Xu_2019_Modeling_human_RNA_spliceosome_mutations_in.pdf | |
License: CC BY-NC-ND 4.0 | |
File access level: Open |
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