| First Author | Gilligan DM | Year | 1999 |
| Journal | Proc Natl Acad Sci U S A | Volume | 96 |
| Issue | 19 | Pages | 10717-22 |
| PubMed ID | 10485892 | Mgi Jnum | J:71029 |
| Mgi Id | MGI:2149009 | Doi | 10.1073/pnas.96.19.10717 |
| Citation | Gilligan DM, et al. (1999) Targeted disruption of the beta adducin gene (Add2) causes red blood cell spherocytosis in mice. Proc Natl Acad Sci U S A 96(19):10717-22 |
| abstractText | Adducins are a family of cytoskeleton proteins encoded by three genes (alpha, beta, gamma). In a comprehensive assay of gene expression, we show the ubiquitous expression of alpha- and gamma-adducins in contrast to the restricted expression of beta-adducin. beta-adducin is expressed at high levels in brain and hematopoietic tissues (bone marrow in humans, spleen in mice). To elucidate adducin's role in vivo, we created beta-adducin null mice by gene targeting, deleting exons 9-13. A 55-kDa chimeric polypeptide is produced from the first eight exons of beta-adducin and part of the neo cassette in spleen but is not detected in peripheral RBCs or brain. beta-adducin null RBCs are osmotically fragile, spherocytic, and dehydrated compared with the wild type, resembling RBCs from patients with hereditary spherocytosis. The lack of beta-adducin in RBCs leads to decreased membrane incorporation of alpha-adducin (30% of normal) and unexpectedly promotes a 5-fold increase in gamma-adducin incorporation into the RBC membrane skeleton. This study demonstrates adducin's importance to RBC membrane stability in vivo. |
