|
|
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.
 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. S. Bhat, N. V. Thuse, H. G. Lubree, C. V. Joglekar, S. S. Naik, L. V. Ramdas, C. Johnston, H. Refsum, C. H. Fall, and C. S. Yajnik
Increases in Plasma Holotranscobalamin Can Be Used to Assess Vitamin B-12 Absorption in Individuals with Low Plasma Vitamin B-12
J. Nutr.,
November 1, 2009;
139(11):
2119 - 2123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Dali-Youcef and E. Andres
An update on cobalamin deficiency in adults
QJM,
January 1, 2009;
102(1):
17 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
