| First Author | Robledo RF | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 9 | Pages | 1804-14 |
| PubMed ID | 20056793 | Mgi Jnum | J:157766 |
| Mgi Id | MGI:4436949 | Doi | 10.1182/blood-2009-07-232199 |
| Citation | Robledo RF, et al. (2010) Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in {alpha}-spectrin-deficient red cells. Blood 115(9):1804-14 |
| abstractText | Five spontaneous, allelic mutations in the alpha-spectrin gene, Spna1, have been identified in mice (spherocytosis [sph], sph(1J), sph(2J), sph(2BC), sph(Dem)). All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals previously unknown consequences of red blood cell (RBC) spectrin deficiency. In sph(3J), a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice site resulting in premature termination of translation. In sph(Ihj), a premature stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly reduced RBC membrane spectrin content, decreased band 3, and absent beta-adducin. Reevaluation of available, previously described sph alleles reveals band 3 and adducin deficiency as well. In sph(4J), a missense mutation occurs in the C-terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia occurs despite minimally decreased membrane spectrin with normal band 3 levels and present, although reduced, beta-adducin. The severity of anemia in sph(4J) indicates that the highly conserved cysteine residue at the C-terminus of alpha-spectrin participates in interactions critical to membrane stability. The data reinforce the notion that a membrane bridge in addition to the classic protein 4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves interactions between spectrin, adducin, and band 3. |
