CLONING OF MOUSE UNCOUPLING PROTEIN-3 CDNA AND 5'-FLANKING REGION, AND ITS GENETIC-MAP

Brown adipose tissue and skeletal muscle are important sites of non-sh ivering thermogenesis. It has been known that UCP1 and UCP2 function a s the main effector of the thermogenesis: the former is expressed excl usively in brown adipose tissue, whereas the latter is distributed wid ely. Recently, the third UCP homologue was discovered in humans, which was designated as UCP3. We now report molecular cloning of full-lengt h mouse UCP3 cDNA and its 5'-flanking genomic region. The mouse UCP3 c DNA sequence predicted a 308-amino acid protein, and the overall ident ity between the mouse and human UCP3 proteins was 85.6%. The mouse UCP 3 amino acid sequence was 54.7% and 73.1% identical to the mouse UCP1 and UCP2, respectively. Expression of the mouse UCP3 was found to be a bundant in skeletal muscle and somewhat less abundant in heart, but wa s minimally expressed in other critical organs. The sequences of 5'-fl anking regions of the mouse UCP1 and UCP3 were very different, resulti ng in different distributions of putative transcriptional factor bindi ng sites. The differences could reflect tissue-specific expression of the UCPs. The mouse Ucp3 gene was mapped near Ucp2 on chromosome 7, su ggesting that the Ucp2 and Ucp3 are clustered genes. This region is bo undary of synteny between human chromosome 11q13 and 11p15. As Solanes et al. reported that both human UCP2 and UCP3 genes are assigned to c hromosome 11q13, the region where the mouse Ucp2 and Ucp3 are localize d is syntenic to human chromosome 11q13. (C) 1998 Elsevier Science B.V . All rights reserved.