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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 (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 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 Social Bookmarking                   What's this? Submitted January 16, 2002 Accepted July 26, 2002 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, Mohandas Narla, and Jane E Barker* The Jackson Laboratory, Bar Harbor, ME, USA NHGRI/Hematopoiesis Section, National Institutes of Health, Bethesda, MD, USA New York Blood Center, New York, NY, USA * Corresponding author; email: jeb{at}jax.org. Tetramers of - and ß-spectrin heterodimers, linked via intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either - or ß-spectrin can result in severe hereditary spherocytosis or elliptocytosis (HS/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 or HE. Here, we describe the molecular alterations in -spectrin and their consequences in sph2BC/sph2BC and sphJ/sphJ erythrocytes. sph2BC is a splicing mutation that initiates skipping of exon 41 and premature protein termination prior to the site required for dimerization of -spectrin with ß-spectrin. sphJ is a nonsense mutation in exon 52 that 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 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. 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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