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X-ray picture of a Fetuin-A knockout mouse (-/-) compared to a wildtype mouse (+/+). The bright dots in the fetuin-A deficient mouse indicate calcified lesions throughout the body.

Fetuins are blood proteins that are made in the liver and secreted into the bloodstream. They belong to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the bloodstream. The best known representative of these carrier proteins is serum albumin, the most abundant protein in the blood plasma of adult animals. Fetuin is more abundant in fetal blood, hence the name "fetuin" (from Latin, fetus). Fetal calf serum contains more fetuin than albumin, while adult serum contains more albumin than fetuin.

Family members[edit]

Human fetuin is synonymous with α2-HS-glycoprotein (genetic symbol AHSG), α2-HS, A2HS, AHS, HSGA, and fetuin-A. Fetuin-A exists as a single-copy gene in the human and mouse genomes. A closely related gene, fetuin-B, also exists in the human, rat, and mouse genomes. Like fetuin-A, fetuin-B is made predominantly by the liver and to a lesser extent by a number of secretory tissues. Fetuins exist in all vertebrate genomes including fish and reptiles. Fetuins are members of a family of proteins that evolved from the protein cystatin by gene duplication and exchange of gene segments. Fetuins thus belong to the cystatin superfamily of proteins. Fetuin relatives within this superfamily are the histidine-rich glycoprotein (HRG) and kininogen (KNG).

Symbol AHSG
Alt. symbols FETUA, A2HS, HSGA
Entrez 197
HUGO 349
OMIM 138680
RefSeq NM_001622
UniProt P02765
Other data
Locus Chr. 3 q27.3
Symbol FETUB
Alt. symbols 16G2, Gugu
Entrez 26998
HUGO 3658
OMIM 605954
RefSeq NM_014375
UniProt Q9UGM5
Other data
Locus Chr. 3 q27.3

Animal studies[edit]

The function of Fetuin-A in the body was determined by gene knockout technology in mice. Knocking out the gene for fetuin-A rendered the mice completely fetuin-A deficient. Feeding a mineral-rich diet to fetuin-A-deficient mice resulted in widespread calcification (ectopic mineralization) of lung, heart, and kidneys in these mice. The calcification became drastically exacerbated when the fetuin-A knockout was combined with the genetic background DBA/2. The mouse strain DBA/2 is known for its proneness to calcify damaged tissues, a process called "dystrophic calcification". Fetuin-A deficiency dramatically increased the calcification proneness of these mice in that all mice sponteneously calcified throughout their body even without a mineral-rich diet or surgical tissue trauma. Fetuin-A is therefore regarded as a potent inhibitor of systemic calcification.

Further reading[edit]

  • Demetriou, M.; Binkert, C.; Sukhu, B.; Tenenbaum, H.C.; Dennis, J.W. (1996). "Fetuin/alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist". The Journal of Biological Chemistry 271 (22): 12755–61. doi:10.1074/jbc.271.22.12755. PMID 8662721. 
  • Jahnen-dechent, W.; Schäfer, C.; Ketteler, M.; McKee, M.D. (2008). "Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification". Journal of molecular medicine 86 (4): 379–89. doi:10.1007/s00109-007-0294-y. PMID 18080808. 
  • Schafer, C.; Heiss, A.; Schwarz, A.; Westenfeld, R.; Ketteler, M.; Floege, J.; Muller-esterl, W.; Schinke, T.; Jahnen-dechent, W. (2003). "The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification". The Journal of Clinical Investigation 112 (3): 357–66. doi:10.1172/JCI17202. PMC 166290. PMID 12897203. 
  • Ketteler, M.; Bongartz, P.; Westenfeld, R.; Wildberger, J.E.; Mahnken, A.H.; Böhm, R.; Metzger, T.; Wanner, C. et al. (2003). "Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study". Lancet 361 (9360): 827–33. doi:10.1016/S0140-6736(03)12710-9. PMID 12642050. 
  • Heiss, A.; Duchesne, A.; Denecke, B.; Grötzinger, J.; Yamamoto, K.; Renné, T.; Jahnen-dechent, W. (2003). "Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles". The Journal of Biological Chemistry 278 (15): 13333–41. doi:10.1074/jbc.M210868200. PMID 12556469.