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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1447-1453. Prepublished online as a Blood First Edition Paper on April 21, 2005; DOI 10.1182/blood-2005-03-1197. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1197v1 106/4/1447    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 He, Q. Articles by Fyfe, J. C. Search for Related Content PubMed PubMed Citation Articles by He, Q. Articles by Fyfe, J. C. Related Collections Gene Expression Free Research Articles Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo Qianchuan He, Mette Madsen, Adam Kilkenney, Brittany Gregory, Erik I. Christensen, Henrik Vorum, Peter Højrup, Alejandro A. Schäffer, Ewen F. Kirkness, Stephan M. Tanner, Albert de la Chapelle, Urs Giger, Søren K. Moestrup, and John C. Fyfe From the Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University (MSU), East Lansing, MI; Department of Medical Biochemistry, University of Aarhus, Aarhus, Denmark; Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Odense, Denmark; National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, MD; Institute for Genomic Research, Rockville, MD; Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus, OH; and Section of Medical Genetics, Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA. Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin. (Blood. 2005;106:1447-1453) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: "Cubam" goes to the dogs David S. Rosenblatt Blood 2005 106: 1146. [Full Text] [PDF] This article has been cited by other articles: D. Shang, X. W. Zheng, M. Niiya, and X. L. Zheng Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts Blood, October 1, 2006; 108(7): 2207 - 2215. [Abstract] [Full Text] [PDF] H. Birn The kidney in vitamin B12 and folate homeostasis: characterization of receptors for tubular uptake of vitamins and carrier proteins Am J Physiol Renal Physiol, July 1, 2006; 291(1): F22 - F36. [Abstract] [Full Text] [PDF]

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