Uncoupling protein homologue: UCP3

Abstract

The present invention relates to the cloned genes which code for uncoupling proteins controlling thermogenesis in human skeletal muscle and heart. A further aspect of the present invention relates to the use of the said genes for correcting dysfunctions of thermogenesis in human skeletal muscle and heart. The present invention makes it possible to exploit novel therapeutic (or preventive) methods for disorders such as obesity or cachexia. As a result of the identification and isolation of the genes coding for UCP3 L and UCP3 S , it is, in effect, possible to develop medicaments which act on the basis of a correction, by gene therapy or by antisense oligonucleotides relating to the sequence of the gene in question or to one of its fragments, of a lack or an excess of UCP3.

1 . DNA fragment, characterized in that it contains the nucleotide sequence depicted in SEQ ID NO 3, the said DNA fragment coding for an uncoupling protein (UCP3 L ) which is characterized by the amino acid sequence depicted in SEQ ID NO 4, or in that it contains a homologous sequence coding for the same amino acid sequence.  
     
     
         2 . DNA fragment according to  claim 1 , characterized in that it originates from human skeletal muscle.  
     
     
         3 . DNA fragment, characterized in that it contains the nucleotide sequence depicted in SEQ ID NO 5, the said DNA fragment coding for an uncoupling protein (UCP3 S ) possessing the amino acid sequence depicted in SEQ ID NO 6, or in that it contains a homologous sequence coding for the same amino acid sequence.  
     
     
         4 . DNA fragment according to  claim 3 , characterized in that it originates from human skeletal muscle.  
     
     
         5 . Uncoupling protein, characterized in that it comprises the amino acid sequence depicted in SEQ ID NO 4.  
     
     
         6 . Uncoupling protein, characterized in that it comprises the amino acid sequence depicted in SEQ ID NO 6.  
     
     
         7 . Recombinant DNA fragment, characterized in that it comprises a DNA sequence according to claims  1 ,  2 ,  3  or  4 , or one of their homologous sequences.  
     
     
         8 . DNA molecule, characterized in that it comprises a cloning vector into which a DNA sequence according to one of  claims 1  to  4  or  7  is inserted.  
     
     
         9 . DNA molecule according to  claim 8 , characterized in that the cloning vector is a plasmid or a phage.  
     
     
         10 . Recombinant DNA molecule according to  claim 9 , characterized in that it consists of the nucleotide sequence depicted in SEQ ID NO 3, inserted into the vector pBluescript SK − .  
     
     
         11 . Recombinant DNA molecule according to  claim 10 , deposited with the ATCC (NO 97999).  
     
     
         12 . Recombinant DNA molecule according to  claim 9 , characterized in that it consists of the nucleotide sequence depicted in SEQ ID NO 5, inserted into the vector pBluescript SK − .  
     
     
         13 . Recombinant DNA molecule according to  claim 12 , deposited with the ATCC (NO 209000).  
     
     
         14 . Microorganism selected from bacteria, yeasts and mammalian cells, characterized in that it contains a recombinant DNA molecule as claimed in  claims 7  to  13 .  
     
     
         15 . Microorganism according to  claim 14 , characterized in that it is an XL1-Blue MRF′ bacterium ( E. coli ).  
     
     
         16 . Pharmaceutical formulation for correcting a lack of UCP3 (UCP3 L , UCP3 S ) by gene therapy, which comprises the gene described in SEQ ID NO 3 or NO 5 and a suitable pharmaceutical vehicle.  
     
     
         17 . Pharmaceutical formulation according to  claim 16 , characterized in that the said gene is contained in a vector chosen from adenoviruses, retroviruses, adeno-associated viruses, herpesvirus, liposomes or DNA plasmids.  
     
     
         18 . Pharmaceutical formulation for correcting an excess of UCP3 (UCP3 L , UCP3 S ), characterized in that it comprises as active principle, antisense oligonucleotides relating to fragments of the sequences of UCP3 L  or of UCP3 S .