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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3233-3240. Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-08-2813. This Article Full Text (PDF) All Versions of this Article: 2003-08-2813v1 103/8/3233    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 Peters, L. L Articles by Churchill, G. C Search for Related Content PubMed PubMed Citation Articles by Peters, L. L Articles by Churchill, G. C Social Bookmarking                   What's this? Submitted August 15, 2003 Accepted December 10, 2003 Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band 3 deficiency Luanne L Peters*, Rebecca A Swearingen, Sabra G Andersen, Babette Gwynn, Amy J Lambert, Renhua Li, Samuel E Lux, and Gary C Churchill The Jackson Laboratory, Bar Harbor, ME, USA Hematology/Oncology, Chldren's Hospital and the Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA * Corresponding author; email: luanne{at}jax.org. Defects in red blood cell (RBC) membrane skeleton components cause hereditary spherocytosis (HS). Clinically, HS varies significantly even among individuals with identical gene defects, illustrating the profound effects of genetic background on disease severity. We exploited a new spontaneous mouse model, wan, which arose on the inbred C3H/HeJ strain, to identify quantitative trait loci (QTL) that modify the HS phenotype. Homozygous wan mice have severe HS due a complete deficiency of erythroid band 3. A QTL analysis of RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin content (MCHC) was performed in wan/wan mice from an F2 intercross between C3H/HeJ-+/wan and CAST/Ei-+/+ F1 hybrids. Hematological and survival data from C3H, CAST/Ei F2 wan homozygotes support the hypothesis that genetic modifiers significantly influence the band 3 null HS phenotype. Significant QTL were identified for the MCV trait only, suggesting that RBC membrane characteristics are a target for modifier gene action. The most significant QTL, Hsm1 (hereditary spherocytosis modifier 1), localizes to mouse Chromosome 12 and is dominant. The peak LOD score was obtained with a marker for Spnb1 encoding erythroid -spectrin, an obvious candidate gene. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. A. Anong, T. Franco, H. Chu, T. L. Weis, E. E. Devlin, D. M. Bodine, X. An, N. Mohandas, and P. S. Low Adducin forms a bridge between the erythrocyte membrane and its cytoskeleton and regulates membrane cohesion Blood, August 27, 2009; 114(9): 1904 - 1912. [Abstract] [Full Text] [PDF] 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] R. F. Robledo, S. L. Ciciotte, B. Gwynn, K. E. Sahr, D. M. Gilligan, N. Mohandas, and L. L. Peters Targeted deletion of {alpha}-adducin results in absent {beta}- and {gamma}-adducin, compensated hemolytic anemia, and lethal hydrocephalus in mice Blood, November 15, 2008; 112(10): 4298 - 4307. [Abstract] [Full Text] [PDF]

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