Summary of hematopoietic changes observed in mouse models of mutant splicing factors
| Gene . | Mutation . | Mouse model . | WBC . | RBC . | PLT . | HSPCs . | Competitive repopulation . | MDS/AML . | Pre-mRNA splicing . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|
| Sf3b1 | K700E | Knockin (activated by cre) | = | ↓ Hg ↑ MCV | = | ↑54 ↓55 (LT-HSCs) = (MPPs)54,55 | ↓ | MDS-like (erythroid dysplasia) | Alternative 3′ SS | 54, 55 |
| Srsf2 | P95H | Knockin (activated by cre) | ↓ | ↓ Hg ↑ MCV | = | ↑ (LSK) | ↓ | MDS-like (multilineage dysplasia) | Altered affinity for ESE motif SSNG | 53 |
| U2AF1 | S34F | Transgenic (DOX inducible) | ↓ | = | = | ↑ (LSK) | ↓ | No | Altered 3′ consensus sequence at −3 bp | 52 |
| Gene . | Mutation . | Mouse model . | WBC . | RBC . | PLT . | HSPCs . | Competitive repopulation . | MDS/AML . | Pre-mRNA splicing . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|
| Sf3b1 | K700E | Knockin (activated by cre) | = | ↓ Hg ↑ MCV | = | ↑54 ↓55 (LT-HSCs) = (MPPs)54,55 | ↓ | MDS-like (erythroid dysplasia) | Alternative 3′ SS | 54, 55 |
| Srsf2 | P95H | Knockin (activated by cre) | ↓ | ↓ Hg ↑ MCV | = | ↑ (LSK) | ↓ | MDS-like (multilineage dysplasia) | Altered affinity for ESE motif SSNG | 53 |
| U2AF1 | S34F | Transgenic (DOX inducible) | ↓ | = | = | ↑ (LSK) | ↓ | No | Altered 3′ consensus sequence at −3 bp | 52 |
=, no change; cre, cre-recombinase; DOX, doxycycline; Hg, hemoglobin; LKS: Lin<low>, Kit+, Sca1+; LT-HSC, Lin<low>, Kit+, Sca1+, CD48−, CD150+ or Lin<low>, Kit+, Sca1+, CD34−, CD135−; MCV, mean corpuscular volume; PLT, platelet; RBC, red blood cell; WBC, white blood cell.