Mitochondrial efficiency: lessons learned from transgenic mice

Metabolic research has, like most areas of research in the life sciences, b een affected dramatically by the application of transgenic technologies. Wi thin the specific area of bioenergetics it has been thought that transgenic approaches in mice would provide definitive proof for some longstanding me tabolic theories and assumptions. Here we review a number of transgenic app roaches that have been used in mice to address theories of mitochondrial ef ficiency. The focus is largely on genes that affect the coupling of energy substrate oxidation to ATP synthesis, and thus, mice in which the uncouplin g protein (Ucp) genes are modified are discussed extensively. Transgenic ap proaches have indeed provided proof-of-concept in some instances, but in ma ny other instances they have yielded results that are in contrast to initia l hypotheses. Many studies have also shown that genetic background can affe ct phenotypic outcomes, and that the upregulated expression of genes that a re related to the modified gene often complicates the interpretation of fin dings. (C) 2001 Elsevier Science B.V. All rights reserved.