Submitted on October 23, 2007
Revised on April 1, 2009
Accepted on April 9, 2009
An intronic single base exchange leads to a brown adipose tissue specific loss of Ucp3 expression and an altered body mass trajectory
Tobias Fromme1*, Christoph Hoffmann1, Kerstin Nau2, Jan Rozman1, Kathrin Reichwald3, Michael Utting3, Matthias Platzer3, and Martin Klingenspor1
1 Technische Universität München
2 Philipps University Marburg
3 Fritz Lipmann Institute
* To whom correspondence should be addressed. E-mail: tobias.fromme{at}wzw.tum.de.
Uncoupling protein 3 (Ucp3) is a transport protein of the inner mitochondrial membrane and presumably implicated in the maintenance or tolerance of high lipid oxidation rates. Ucp3 is predominantly expressed in skeletal muscle and brown adipose tissue and regulated by a transcription factor complex involving PPAR
, MyoD and Coup-TFII. By analysis of a mutant Djungarian hamster model lacking Ucp3 transcription specifically in brown adipose tissue we identified a putative transcription factor binding site which confers tissue specificity. A naturally occurring, intronic point mutation disrupting this site leads to brown adipose tissue specific loss of Ucp3 expression and an altered body weight trajectory. Our findings provide insight into tissue specific Ucp3 regulation and for the first time unambiguously demonstrate that changes in Ucp3 expression can interfere with body weight regulation.
