{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:57:21Z","timestamp":1782907041299,"version":"3.54.5"},"reference-count":50,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tetramers of \u03b1- and \u03b2-spectrin heterodimers, linked by intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either \u03b1- or \u03b2-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 \u03b1-spectrin gene, Spna1, on chromosome 1 and cause severe HS and HE. Here we describe the molecular alterations in \u03b1-spectrin and their consequences insph2BC\/sph2BC andsphJ\/sphJerythrocytes. A splicing mutation, sph2BC initiates the skipping of exon 41 and premature protein termination before the site required for dimerization of \u03b1-spectrin with \u03b2-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. Insph2BC\/sph2BC, barely perceptible levels of messenger RNA and consequent decreased synthesis of \u03b1-spectrin protein are primarily responsible for the resultant hemolysis. By contrast, sphJ\/sphJmice synthesize the truncated \u03b1-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. ThesphJdeletion 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 \u03b1-spectrin is crucial to the stability of the junctional complex.<\/jats:p>","DOI":"10.1182\/blood-2002-01-0113","type":"journal-article","created":{"date-parts":[[2002,12,16]],"date-time":"2002-12-16T21:02:38Z","timestamp":1040072558000},"page":"325-330","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":18,"title":["Mutations in the murine erythroid \u03b1-spectrin gene alter spectrin mRNA and protein levels and spectrin incorporation into the red blood cell membrane skeleton"],"prefix":"10.1182","volume":"101","author":[{"given":"Nancy J.","family":"Wandersee","sequence":"first","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie S.","family":"Birkenmeier","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Bodine","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narla","family":"Mohandas","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Barker","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021223211099800_B1","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1182\/blood.V51.6.1149.1149","article-title":"Marked reduction of spectrin in hereditary spherocytosis in the common house mouse.","volume":"51","author":"Greenquist","year":"1978","journal-title":"Blood."},{"key":"2020021223211099800_B2","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/0092-8674(84)90408-2","article-title":"Spectrin-deficient inherited hemolytic anemias in the mouse: characterization by spectrin synthesis and mRNA 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