Publikationsserver der RWTH Aachen University
Biochemische und funktionelle Charakterisierung einer gerichteten Gendeletion (Knockout) von Fetuin-A in Mäusen
Abstract
dc:descriptionAn elevated calcium phosphate product is regarded as the main reason for pathological calcification in arteries and soft tissues, as seen in chronic renal failure. However, recent studies show that proteins also low molecular weight compounds act as inhibitiors of unwanted mineral precipitation. The serum protein fetuin-A/a2-HS glycoprotein (Ahsg) can transiently inhibit the calcium phosphate precipitation in vitro by binding the crystal nucleus, inhibiting it's growth and forming a soluble colloid. The backcrossing of Ahsg knockout mice onto two defined inbred strains resulted in two phenotypes. While the Ahsg deficiency on the calcification-resistant C57BL/6 (B6) strain showed no spontaneous calcification phenotype, widespread and systemic ectopic calcification was observed onto the sensitive strain DBA/2 (D2) in contrast to D2 wildtype mice. Alizarin red staining of adult mice detected calcium precipitates in heart, lung, kidney, sexual organs, skin and tongue. The damage of the affected organs led also to an increased mortality and a depressed breeding performance. The renal damage was associated with an increased serum creatinine, albuminuria and a secondary hyperparathyreoidism. In 1-month old D2, Ahsg -/- animals calcifications were detected in heart and lung but not in the kidney cortex. The renal function parameters creatinine and urea as well as calcium and phosphate concentrations in serum were also normal at this timepoint. These data indicate that the spontaneous systemic calcification phenotype in the D2, Ahsg -/- mice was caused by a deficiency of fetuin-A as an important soluble crystallization-inhibitor and was subsequently aggravated by a calcification-dependent renal insufficiency. A comparison of D2 and B6, Ahsg -/- animals suggested that there are additional genetic components that contribute to the phenotype. The decreased magnesium concentration in the D2 strain could be one modulator because magnesium ions - as fetuin-A - can inhibit crystal growth.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2004
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Schäfer, Cora
- Contributors dc:contributor
-
- Jahnen-Dechent, Wilhelm
Subjects
dc:subject × 6Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:59296