Table 1.
Germline genetically engineered murine models investigating the function of ASXL family members in cancer and development
| Mouse model | Biological phenotype | Epigenetic alterations | References |
|---|---|---|---|
| Asxl1tm1Bc mutant | Partial embryonic lethality, alterations of the axial skeleton, early death, reduction in body weight and thymus, splenomegaly; defects in frequency of differentiation of lymphoid and myeloid progenitors but no hematological phenotype | Hoxa4 and Hoxa7 repression | Fisher et al. 2010a,b |
| EIIa-cre Asxl1fl/fl | 100% embryonic lethality, craniofacial abnormalities | Not described | Abdel-Wahab et al. 2013 |
| Mx1-cre Asxl1fl/fl | MDS-like phenotype; aggressive MDS | Reduced global H3K27me3, increase expression of HoxA genes | |
|
Asxl1−/− (Asxl1:nlacZ/nGFP) |
80% embryonic lethality, 78% of newborn died after 1 day, developmental abnormalities; MDS-like disease | Not described | Wang et al. 2014 |
|
Asxl1+/– (Asxl1:nlacZ/nGFP) |
Haploinsufficiency sufficient for the development of MDS-like and MDS/MPN-like disease | Increased expression of HoxA genes (HoxA5, 7, 9, and 10); decrease of global levels of H3K27me3 and H3K4me3 | |
| Asxl1tm1a | Partial embryonic lethality, reduced body weight and display cleft palate, anophthalmia, ventricular septal defects, lung defects | Not described | McGinley et al. 2014 |
| Asxl1-null mice | Defects in kidney size and glomerular podocyte morphology | Not described | Moon et al. 2015 |
| Germline Bap1−/− | Embryonic lethality | Not described | Dey et al. 2012 |
| Cre-ERT2 Bap1fl/fl | MDS/CMML-like disease | ||
| Asxl2 gene trap mutant mice (Asxl2Gt(AQ0356)) | Partially embryonic lethal, transformation in the axial skeleton, reduced body weight, congenital heart malformations, low bone mineral density, osteopetrosis, lipodystrophy, insulin resistance | Reduction in the bulk level of H3K27me3 in cardiac tissue | Baskind et al. 2009; Farber et al. 2011; Lai et al. 2012; Lai and Wang 2013; Izawa et al. 2015 |
| Mx1-cre Asxl2fl/fl | Cytopenias (leukopenia, thrombocytopenia), defect in hematopoietic self-renewal | Reduction in H3K4me1 | Micol et al. 2015 |
CMML, Chronic myelomonocytic leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm.