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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-01-0113. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0113v1 101/1/325    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wandersee, N. J. Articles by Barker, J. E. Search for Related Content PubMed PubMed Citation Articles by Wandersee, N. J. Articles by Barker, J. E. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 325-330 RED CELLS Mutations in the murine erythroid -spectrin gene alter spectrin mRNA and protein levels and spectrin incorporation into the red blood cell membrane skeleton Nancy J. Wandersee, Connie S. Birkenmeier, David M. Bodine, Narla Mohandas, and Jane E. Barker From The Jackson Laboratory, Bar Harbor, ME; the National Human Genome Research Institute/Hematopoiesis Section, National Institutes of Health, Bethesda, MD; and the New York Blood Center, NY. Tetramers of - and -spectrin heterodimers, linked by intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either - or -spectrin can result in severe hereditary spherocytosis (HS) or hereditary elliptocytosis (HE) in mice and humans. Four mouse mutations, sph, sphDem, sph2BC, and sphJ, affect the erythroid -spectrin gene, Spna1, on chromosome 1 and cause severe HS and HE. Here we describe the molecular alterations in -spectrin and their consequences in sph2BC/sph2BC and sphJ/sphJ erythrocytes. A splicing mutation, sph2BC initiates the skipping of exon 41 and premature protein termination before the site required for dimerization of -spectrin with -spectrin. A nonsense mutation in exon 52, sphJ eliminates the COOH-terminal 13 amino acids. Both defects result in instability of the red cell membrane and loss of membrane surface area. In sph2BC/sph2BC, barely perceptible levels of messenger RNA and consequent decreased synthesis of -spectrin protein are primarily responsible for the resultant hemolysis. By contrast, sphJ/sphJ mice synthesize the truncated -spectrin in which the 13-terminal amino acids are deleted at higher levels than normal, but they cannot retain this mutant protein in the cytoskeleton. The sphJ deletion is near the 4.1/actin-binding region at the junctional complex providing new evidence that this 13-amino acid segment at the COOH-terminus of -spectrin is crucial to the stability of the junctional complex. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Rank, R. Sutton, V. Marshall, R. J. Lundie, J. Caddy, T. Romeo, K. Fernandez, M. P. McCormack, B. M. Cooke, S. J. Foote, et al. Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant Blood, April 2, 2009; 113(14): 3352 - 3362. [Abstract] [Full Text] [PDF] S. Metral, B. Machnicka, S. Bigot, Y. Colin, D. Dhermy, and M.-C. Lecomte {alpha}II-Spectrin Is Critical for Cell Adhesion and Cell Cycle J. Biol. Chem., January 23, 2009; 284(4): 2409 - 2418. [Abstract] [Full Text] [PDF] X. Pei, X. Guo, R. Coppel, N. Mohandas, and X. An Plasmodium falciparum Erythrocyte Membrane Protein 3 (PfEMP3) Destabilizes Erythrocyte Membrane Skeleton J. Biol. Chem., September 14, 2007; 282(37): 26754 - 26758. [Abstract] [Full Text] [PDF] N. J. Wandersee, S. C. Olson, S. L. Holzhauer, R. G. Hoffmann, J. E. Barker, and C. A. Hillery Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis Blood, January 15, 2004; 103(2): 710 - 716. [Abstract] [Full Text] [PDF] N. Monnier, A. Ferreiro, I. Marty, A. Labarre-Vila, P. Mezin, and J. Lunardi A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia Hum. Mol. Genet., May 15, 2003; 12(10): 1171 - 1178. [Abstract] [Full Text] [PDF]

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