کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833664 | 1065805 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs
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کلمات کلیدی
CubilinqPCRAMNMMAGIFmethylmalonic acidReverse transcriptase - ترانس کریپتاز معکوس یا وارونویسCub - تولهInborn error - خطا در بارداریgastric intrinsic factor - عامل ذاتی معدهMethylmalonic aciduria - متیل مالون اسیدوریاAnimal model - مدل حیوانیBorder Collie - مرجانی کولیquantitative polymerase chain reaction - واکنش زنجیره ای پلیمراز کمیvitamin B12 - ویتامین ب۱۲Single nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Â Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~Â 10 fold and ~Â 20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 4, August 2013, Pages 390-396
Journal: Molecular Genetics and Metabolism - Volume 109, Issue 4, August 2013, Pages 390-396
نویسندگان
John C. Fyfe, Shelby L. Hemker, Patrick J. Venta, Caitlin A. Fitzgerald, Catherine A. Outerbridge, Sherry L. Myers, Urs Giger,