Hyperhomocysteinemia. Current overview and contribution of mice to research on the topic

Homocysteine is an amino acid whose plasma levels are associated with the development of vascular, neurologic and reproductive diseases. Plasma levels show a wide range of values according to age, sex, race and other environmental factors. The present review discusses homocysteine metabolism and physiopathology and the clinical consequences of increased levels of this substance. Special emphasis has been placed on the use of mice as an experimental animal model in this field, since their use has unveiled the contribution of dietary modifications on plasma homocysteine levels. These findings, together with the generation of genetically-modified mice as models of hyperhomocysteinemia, are allowing rapid progress to be made in the characterization of the in vivo molecular mechanisms of homocysteine action. Crosses among these genetically-modified mice and others with different deleted genes will increase knowledge of the influence of the combination of several risk factors on pathological development. In these models, research into new environmental or pharmacological factors may yield results that could explain epidemiological findings in humans and help in the design of new treatments for specific clinical settings. © 2009 Elsevier España, S.L. y SEA.