{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:08:55Z","timestamp":1784257735353,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Linkage between transmembrane proteins and the spectrin-based cytoskeleton is necessary for membrane elasticity of red blood cells. Mutations of the proteins that mediate this linkage result in various types of hemolytic anemia. Here we report a novel N-ethyl-N-nitrosourea\u2212induced mutation of ankyrin-1, named hema6, which causes hereditary spherocytosis in mice through a mild reduction of protein expression. The causal mutation was traced to a single nucleotide transition located deep into intron 13 of gene Ank1. In vitro minigene splicing assay revealed two abnormally spliced transcripts containing cryptic exons from fragments of Ank1 intron 13. The inclusion of cryptic exons introduced a premature termination codon, which leads to nonsense-mediated decay of the mutant transcripts in vivo. Hence, in homozygous mice, only wild-type ankyrin-1 is expressed, albeit at 70% of the level in wild-type mice. Heterozygotes display a similar hereditary spherocytosis phenotype stemming from intermediate protein expression level, indicating the haploinsufficiency of the mutation. Weakened linkage between integral transmembrane protein, band 3, and underlying cytoskeleton was observed in mutant mice as the result of reduced high-affinity binding sites provided by ankyrin-1. Hema6 is the only known mouse mutant of Ank1 allelic series that expresses full-length canonical ankyrin-1 at a reduced level, a fact that makes it particularly useful to study the functional impact of ankyrin-1 quantitative deficiency.<\/jats:p>","DOI":"10.1534\/g3.113.007013","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T16:55:29Z","timestamp":1381251329000},"page":"1687-1695","source":"Crossref","is-referenced-by-count":8,"title":["A Deep Intronic Mutation in the Ankyrin-1 Gene Causes Diminished Protein Expression Resulting in Hemolytic Anemia in Mice"],"prefix":"10.1093","volume":"3","author":[{"given":"Hua","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PengXiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Arimatsu","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Department of Oral Bioscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan"},{"name":"Division of Oral Science for Health Promotion, Laboratory of Periodontology and Immunology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tabeta","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Department of Oral Bioscience, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Division of Oral Science for Health Promotion, Laboratory of Periodontology and Immunology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Krieg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093"},{"name":"Department of Radiotherapy, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,1]]},"reference":[{"key":"2021041906454018800_bib1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1186\/1756-0500-5-577","article-title":"ENU-induced phenovariance in mice: inferences from 587 mutations.","volume":"5","author":"Arnold","year":"2012","journal-title":"BMC Res. 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