Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene
Details
Publication Year 2006-10-31, Volume 103, Issue #44, Page 16442-16447
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
An N-ethyl-N-nitrosourea mutagenesis screen in mice was performed to isolate regulators of circulating platelet number. We report here recessive thrombocytopenia and kidney disease in plt1 mice, which is the result of a severe but partial loss-of-function mutation in the gene encoding glycoprotein-N-acetylgalactosamine-3-beta-galactosyltransferase (C1GalT1), an enzyme essential for the synthesis of extended mucin-type O-glycans. Platelet half-life and basic hemostatic parameters were unaffected in plt1/plt1 mice, and the thrombocytopenia and kidney disease were not attenuated on a lymphocyte-deficient rag1-null background. underglycosylated proteins in plt1/plt1 platelets and the kidney, respectively, implying that these are key targets for ClGaIT1, appropriate glycosylation of which is essential for platelet production and kidney function. Compromised ClGaIT1 activity has been associated with immune-mediated diseases in humans, most notably Tin syndrome and IgA nephropathy. The disease in plt1/plt1 mice suggests that, in addition to immune-mediated effects, intrinsic C1Gal-T1 deficiency in megakaryocytes and the kidney may contribute to pathology.
Publisher
NATL ACAD SCIENCES
Keywords
core 1 galactosyltransferase ; N-ethyl-N-nitrosourea mutagenesis ; nephropathy ; platelet
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2006-10-31 12:00:00
Last Modified: 2014-12-23 01:41:37
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