| First Author | Ma S | Year | 2018 |
| Journal | Cell | Volume | 173 |
| Issue | 2 | Pages | 443-455.e12 |
| PubMed ID | 29576450 | Mgi Jnum | J:261124 |
| Mgi Id | MGI:6153426 | Doi | 10.1016/j.cell.2018.02.047 |
| Citation | Ma S, et al. (2018) Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection. Cell 173(2):443-455.e12 |
| abstractText | Hereditary xerocytosis is thought to be a rare genetic condition characterized by red blood cell (RBC) dehydration with mild hemolysis. RBC dehydration is linked to reduced Plasmodium infection in vitro; however, the role of RBC dehydration in protection against malaria in vivo is unknown. Most cases of hereditary xerocytosis are associated with gain-of-function mutations in PIEZO1, a mechanically activated ion channel. We engineered a mouse model of hereditary xerocytosis and show that Plasmodium infection fails to cause experimental cerebral malaria in these mice due to the action of Piezo1 in RBCs and in T cells. Remarkably, we identified a novel human gain-of-function PIEZO1 allele, E756del, present in a third of the African population. RBCs from individuals carrying this allele are dehydrated and display reduced Plasmodium infection in vitro. The existence of a gain-of-function PIEZO1 at such high frequencies is surprising and suggests an association with malaria resistance. |
