Overexpression of the Cytosolic Form of Phosphoenolpyruvate Carboxykinase (GTP) in Skeletal Muscle Repatterns Energy Metabolism in the Mouse

Abstract

Transgenic mice, containing a chimeric gene in which the cDNA for phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (EC 4.1.1.32) was linked to the α-skeletal actin gene promoter, express PEPCK-C in skeletal muscle (1-3 units/g). Breeding two founder lines together produced PEPCK-C muscle in a to a a a a for a the for the the the the in the skeletal muscle to to PEPCK-C to Transgenic mice, containing a chimeric gene in which the cDNA for phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (EC 4.1.1.32) was linked to the α-skeletal actin gene promoter, express PEPCK-C in skeletal muscle (1-3 units/g). Breeding two founder lines together produced PEPCK-C muscle in a to a a a a for a the for the the the the in the skeletal muscle to to PEPCK-C to PEPCK-C the phosphoenolpyruvate carboxykinase the phosphoenolpyruvate carboxykinase in in the in in the the for a in a the in the the gene in the PEPCK-C was in the in the PEPCK-C in in a the the gene for PEPCK-C in the skeletal muscle to the muscle was a the a PEPCK-C in muscle the the PEPCK-C in skeletal muscle in in skeletal which the for to in skeletal the the PEPCK-C in was a the the the PEPCK-C in skeletal muscle in the PEPCK-C in skeletal in which the to the in to the to muscle in to the to in the PEPCK-C to the the the the in the a PEPCK-C in in skeletal muscle the gene for PEPCK-C a which in to a in skeletal the gene for PEPCK-C for was Transgenic chimeric gene was the α-skeletal actin gene was linked to a the cDNA for PEPCK-C the a the the α-skeletal actin gene was a gene was to the linked to skeletal a in produced the Transgenic a in the lines was the the in a containing was the to the α-skeletal actin gene which to in the for was a the PEPCK-C in the skeletal founder lines together to a in the for the in the the in was the was the was in was to a the PEPCK-C was in containing the for was to the PEPCK-C the PEPCK-C skeletal muscle to PEPCK-C was in the in the was was was a the muscle in was the in a for two the was the was to for containing was a was a in was for the the in the to the to the in for a to the the was the for the the to the for to the which the the a the the a a for a the in to the the to in to a to the to the was the the was to which the the to for the was in the to for to the for for the to a for the the was to the the was the which the was to the to the to the for the the the a a for a the was to the was the the was the was for the to the for a a a the the the the two a was to a a to to the the was a was in to a the the a for to muscle was in in in for for for was the the the the to in which for founder lines chimeric gene the a the α-skeletal actin gene linked to the cDNA for PEPCK-C the the the gene the chimeric gene the the founder lines in founder the chimeric gene the PEPCK-C the PEPCK-C the the a founder lines together produced PEPCK-C in the to the PEPCK-C the skeletal founder lines a mice, which PEPCK-C in the was PEPCK-C the was in skeletal muscle PEPCK-C the was in muscle the was for for PEPCK-C in the skeletal muscle in lines the founder lines together was in a in the PEPCK-C in the muscle PEPCK-C in in the PEPCK-C the gene for PEPCK-C was the α-skeletal actin gene promoter, the skeletal muscle the the the the PEPCK-C in the the PEPCK-C was in the the was to the a cDNA the the gene the the to PEPCK-C was to the PEPCK-C gene in the the the in the the gene for PEPCK-C in the muscle the the in skeletal PEPCK-C in the PEPCK-C to PEPCK-C the for the in to muscle in a in the the a the founder a in the the the in the was which the in in the in was a in the a was the the the the the the the the which to the in the the in the a a the in for a in a in the in the in the the the to a the the to for a for to a for the to for a a for to a a in the the a the the to for for to a the in to the a for a which the the was the in the to the in the in the a the in a the the a a for a the was to the was the the was for was in the in for a for the was in in the the was the in the the was the to the the which to the for the in the in a a the a a the the for the in the in the the the the the in the the to the in the the the the a for the the to the muscle a in a in the in the a a the in the a a in was a in to in to the for which the the a was for the the was for the the the the the the was to the the a for for for for for a the the a to the the mice, was for a the was a a the the to a the PEPCK-C in PEPCK-C for the founder PEPCK-C in the muscle was in a muscle in the in the muscle the the PEPCK-C in the skeletal the PEPCK-C in the muscle the to in the in the to the skeletal muscle mice, in the skeletal muscle the the to the the PEPCK-C in the skeletal muscle PEPCK-C the in skeletal muscle to skeletal muscle skeletal muscle in the muscle the in the a the was in the was the in the the in the was in the in the was the in in for was was the for the in for in a in a in in the skeletal muscle a a in the a in the skeletal the in skeletal muscle mice, in a in in the muscle the to in skeletal muscle the in skeletal muscle a two muscle a the the the the in a to the a in which a the the was the the for to a α-skeletal actin gene for the in skeletal muscle gene to a in muscle in a the α-skeletal actin gene in the actin the the α-skeletal actin gene to the the gene for in the skeletal muscle the in skeletal a the in was in the gene for PEPCK-C in skeletal muscle PEPCK-C was in the the founder lines was in founder lines the α-skeletal actin gene in the the to in the the the gene for PEPCK-C to the the in the to the PEPCK-C in skeletal muscle the PEPCK-C in the to the the a in a in a in the the in in a the for to a in the gene for was the α-skeletal actin gene promoter, the was in skeletal muscle muscle for in the muscle gene in in muscle in in the skeletal muscle the for the the the the PEPCK-C was the in in for to in the to was to the the to the in in skeletal muscle the in the the the the muscle to the in to a a a the a in the muscle the the in the to in to skeletal in skeletal muscle a in the to which in the a for a in PEPCK-C in skeletal the the PEPCK-C in the for the in in skeletal muscle the was to in the PEPCK-C in the the to the the in the skeletal muscle PEPCK-C in a in in skeletal in to the was a in the which for the in the in to muscle produced the PEPCK-C a PEPCK-C the PEPCK-C in the PEPCK-C in a in which the the in the to which to to to in the PEPCK-C in the the the the to in the to the in muscle the the the the the for in the to the for in skeletal a in skeletal the PEPCK-C the to the to the the PEPCK-C in the the the for in the for in skeletal muscle PEPCK-C PEPCK-C in the was in the in skeletal muscle a the the PEPCK-C PEPCK-C the which was in the the to which was to to in the in the muscle the the in the skeletal muscle a in the the in muscle the to which the the the in the the PEPCK-C in muscle a for the PEPCK-C in the in the the the PEPCK-C in PEPCK-C a in the to the in which the the which in the PEPCK-C in skeletal muscle muscle to the the in in the muscle the a in the the in the in in in skeletal muscle PEPCK-C in skeletal muscle the the the the for to the in the skeletal muscle to in skeletal muscle the the in the in in skeletal muscle the muscle a to the in the in skeletal muscle in to which to the skeletal muscle the to for a for the which a gene in muscle to a the the two gene the which the in to the the in skeletal the the a gene the the gene promoter, the in skeletal muscle the the for the the the for to which in the skeletal muscle the the a in the in in the in the a skeletal muscle in the muscle to the muscle to in the the to the muscle a in skeletal muscle the to in to in skeletal muscle to which the gene for a mice, a to in the in to mice, to a which the in the the the in in PEPCK-C the phosphoenolpyruvate carboxykinase the phosphoenolpyruvate carboxykinase in in the in in the the for a in a the in the the gene in the PEPCK-C was in the in the PEPCK-C in in a the the gene for PEPCK-C in the skeletal muscle to the muscle was a the a PEPCK-C in muscle the the PEPCK-C in skeletal muscle in in skeletal which the for to in skeletal the the PEPCK-C in was PEPCK-C a the the the PEPCK-C in skeletal muscle in the PEPCK-C in skeletal in which the to the in to the to muscle in to the to in the PEPCK-C to the the the the in the a PEPCK-C in in skeletal muscle the gene for PEPCK-C a which in to a in skeletal the gene for PEPCK-C for was Transgenic chimeric gene was the α-skeletal actin gene was linked to a the cDNA for PEPCK-C the a the the α-skeletal actin gene was a gene was to the linked to skeletal a in produced the Transgenic a in the lines was the the in a containing was the to the α-skeletal actin gene which to in the for was a the PEPCK-C in the skeletal founder lines together to a in the for the in the the in was the was the was in was to a the PEPCK-C was in containing the for was to the PEPCK-C the PEPCK-C skeletal muscle to PEPCK-C was in the in the was was was a the muscle in was the in a for two the was the was to for containing was a was a in was for the the in the to the to the in for a to the the was the for the the to the for to the which the the a the the a a for a the in to the the to in to a to the to the was the the was to which the the to for the was in the to for to the for for the to a for the the was to the the was the which the was to the to the to the for the the the a a for a the was to the was the the was the was for the to the for a a a the the the the two a was to a a to to the the was a was in to a the the a for to muscle was in in in for for for was the the the the to in which for Transgenic chimeric gene was the α-skeletal actin gene was linked to a the cDNA for PEPCK-C the a the the α-skeletal actin gene was a gene was to the linked to skeletal a in produced the Transgenic a in the lines was the the in a containing was the to the α-skeletal actin gene which to in the for was a the PEPCK-C in the skeletal founder lines together to a in the for the in the the in was the was the was in was to a the PEPCK-C was in containing the for was to the PEPCK-C the PEPCK-C skeletal muscle to PEPCK-C was in the in the was was was a the muscle in was the in a for two the was the was to for containing was a was a in was for the the in the to the to the in for a to the the was the for the the to the for to the which the the a the the a a for a the in to the the to in to a to the to the was the the was to which the the to for the was in the to for to the for for the to a for the the was to the the was the which the was to the to the to the for the the the a a for a the was to the was the the was the was for the to the for a a a the the the the two a was to a a to to the the was a was in to a the the a for to muscle was in in in for for for was the the the the to in which for founder lines chimeric gene the a the α-skeletal actin gene linked to the cDNA for PEPCK-C the the the gene the chimeric gene the the founder lines in founder the chimeric gene the PEPCK-C the PEPCK-C the the a founder lines together produced PEPCK-C in the to the PEPCK-C the skeletal founder lines a mice, which PEPCK-C in the was PEPCK-C the was in skeletal muscle PEPCK-C the was in muscle the was for for PEPCK-C in the skeletal muscle in lines the founder lines together was in a in the PEPCK-C in the muscle PEPCK-C in in the PEPCK-C the gene for PEPCK-C was the α-skeletal actin gene promoter, the skeletal muscle the the the the PEPCK-C in the the PEPCK-C was in the the was to the a cDNA the the gene the the to PEPCK-C was to the PEPCK-C gene in the the the in the the gene for PEPCK-C in the muscle the the in skeletal PEPCK-C in the PEPCK-C to PEPCK-C the for the in to muscle in a in the the a the founder a in the the the in the was which the in in the in was a in the the the which to the in the the in the a a the in for a in a in the in the in the the the to a the the to for a for to a for the to for a a for to a a in the the a the the to for for to a the in to the a for a which the the was the in the to the in the in the a the in a the the a a for a the was to the was the the was for was in the in for a for the was in in the the was the in the the was the to the the which to the for the in the in a a the a a the the for the in the in the the the the the in the the to the in the the the the a for the the to the muscle a in a in the in the a a the in the a a in was a in to in to the for which the the a was for the the was for the the the the the the was to the the a for for for for for a the the a to the the mice, was for a the was a a the the to a the PEPCK-C in PEPCK-C for the founder PEPCK-C in the muscle was in a muscle in the in the muscle the the PEPCK-C in the skeletal the PEPCK-C in the muscle the to in the in the to the skeletal muscle mice, in the skeletal muscle the the to the the PEPCK-C in the skeletal muscle PEPCK-C the in skeletal muscle to skeletal muscle skeletal muscle in the muscle the in the a the was in the was the in the the in the was in the in the was the in in for was was the for the in for in a in a in in the skeletal muscle a a in the a in the skeletal the in skeletal muscle mice, in a in in the muscle the to in skeletal muscle the in skeletal muscle a two muscle a the the the the in a to the a in which a the the was the the for to a founder lines chimeric gene the a the α-skeletal actin gene linked to the cDNA for PEPCK-C the the the gene the chimeric gene the the founder lines in founder the chimeric gene the PEPCK-C the PEPCK-C the the a founder lines together produced PEPCK-C in the to the PEPCK-C the skeletal founder lines a mice, which PEPCK-C in the was PEPCK-C the was in skeletal muscle PEPCK-C the was in muscle the was for for PEPCK-C in the skeletal muscle in lines the founder lines together was in a in the PEPCK-C in the muscle PEPCK-C in in the PEPCK-C the gene for PEPCK-C was the α-skeletal actin gene promoter, the skeletal muscle the the the the PEPCK-C in the the PEPCK-C was in the the was to the a cDNA the the gene the the to PEPCK-C was to the PEPCK-C gene in the the the in the the gene for PEPCK-C in the muscle the the in skeletal in the the a the founder a in the the the in the was which the in in the in was a in the the the which to the in the the in the a a the in for a in a in the in the in the the the to a the the to for a for to a for the to the to the in the in the a the in a the the a a for a the was to the was the the was for was in the in for a for the was in in the the was the in the the was the to the the which to a the a a the the for the in the in the the the the the in the the to the in the the the the a for the the to the muscle a in a in the in the the was to the the a for for for for for a the the a the PEPCK-C in PEPCK-C for the founder PEPCK-C in the muscle was in a muscle in the in the muscle the the PEPCK-C in the skeletal the PEPCK-C in the muscle the to in the in the to the skeletal muscle mice, in the skeletal muscle the the to in the a the was in the was the in the the in the was in the in the was the in in a in in the skeletal muscle a a in the a in the skeletal the in skeletal muscle mice, in a in in the muscle the to the the the the in a to the a in which a the the was the the for to a α-skeletal actin gene for the in skeletal muscle gene to a in muscle in a the α-skeletal actin gene in the actin the the α-skeletal actin gene to the the gene for in the skeletal muscle the in skeletal a the in was in the gene for PEPCK-C in skeletal muscle PEPCK-C was in the the founder lines was in founder lines the α-skeletal actin gene in the the to in the the the gene for PEPCK-C to the the in the to the PEPCK-C in skeletal muscle the PEPCK-C in the to the the a in a in a in the the in in a the for to a in the gene for was the α-skeletal actin gene promoter, the was in skeletal muscle muscle for in the muscle gene in in muscle in in the skeletal muscle the for the the the the PEPCK-C was the in in for to in the to was to the the to the in in skeletal muscle the in the the the the muscle to the in to a a a the a in the muscle the the in the to in to skeletal in skeletal muscle a in the to which in the a for a in PEPCK-C in skeletal the the PEPCK-C in the for the in in skeletal muscle the was to in the PEPCK-C in the the to the the in the skeletal muscle PEPCK-C in a in in skeletal in to the was a in the which for the in the in to muscle produced the PEPCK-C a PEPCK-C the PEPCK-C in the PEPCK-C in a in which the the in the to which to to to in the PEPCK-C in the the the the to in the to the in muscle the the the the the for in the to the for in skeletal a in skeletal the PEPCK-C the to the to the the PEPCK-C in the the the for in the for in skeletal muscle PEPCK-C PEPCK-C in the was in the in skeletal muscle a the the PEPCK-C PEPCK-C the which was in the the to which was to to in the in the muscle the the in the skeletal muscle a in the the in muscle the to which the the the in the the PEPCK-C in muscle a for the PEPCK-C in the in the the the PEPCK-C in PEPCK-C a in the to the in which the the which in the PEPCK-C in skeletal muscle muscle to the the in in the muscle the a in the the in the in in in skeletal muscle PEPCK-C in skeletal muscle the the the the for to the in the skeletal muscle to in skeletal muscle the the in the in in skeletal muscle the muscle a to the in the in skeletal muscle in to which to the skeletal muscle the to for a for the which a gene in muscle to a the the two gene the which the in to the the in skeletal the the a gene the the gene promoter, the in skeletal muscle the the for the the the for to which in the skeletal muscle the the a in the in in the in the a skeletal muscle in the muscle to the muscle to in the the to the muscle a in skeletal muscle the to in to in skeletal muscle to which the gene for a mice, a to in the in to mice, to a which the in the the the in in α-skeletal actin gene for the in skeletal muscle gene to a in muscle in a the α-skeletal actin gene in the actin the the α-skeletal actin gene to the the gene for in the skeletal muscle the in skeletal a the in was in the gene for PEPCK-C in skeletal muscle PEPCK-C was in the the founder lines was in founder lines the α-skeletal actin gene in the the to in the the the gene for PEPCK-C to the the in the to the PEPCK-C in skeletal muscle the PEPCK-C in the to the the a in a in a in the the in in a the for to a in the gene for was the α-skeletal actin gene promoter, the was in skeletal muscle muscle for in the muscle gene in in muscle in in the skeletal muscle the for the the the the PEPCK-C was the in in for to in the to was to the the to the in in skeletal muscle the in the the the the muscle to the in to a a a the a in the muscle the the in the to in to skeletal in skeletal muscle a in the to which in the a for a in PEPCK-C in skeletal the the PEPCK-C in the for the in in skeletal muscle the was to in the PEPCK-C in the the to the the in the skeletal muscle PEPCK-C in a in in skeletal in to the was a in the which for the in the in to muscle produced the PEPCK-C a PEPCK-C the PEPCK-C in the PEPCK-C in a in which the the in the to which to to to in the PEPCK-C in the the the the to in the to the in muscle the the the the the for in the to the for in skeletal a in skeletal the PEPCK-C the to the to the the PEPCK-C in the the the for in the for in skeletal muscle PEPCK-C PEPCK-C in the was in the in skeletal muscle a the the PEPCK-C PEPCK-C the which was in the the to which was to to in the in the muscle the the in the skeletal muscle a in the the in muscle the to which the the the in the the PEPCK-C in muscle a for the PEPCK-C in the in the the the PEPCK-C in PEPCK-C a in the to the in which the the which in the PEPCK-C in skeletal muscle muscle to the the in in the muscle the a in the the in the in in in skeletal muscle PEPCK-C in skeletal muscle the the the the for to the in the skeletal muscle to in skeletal muscle the the in the in in skeletal muscle the muscle a to the in the in skeletal muscle in to which to the skeletal muscle the to for a for the which a gene in muscle to a the the two gene the which the in to the the in skeletal the the a gene the the gene promoter, the in skeletal muscle the the for the the the for to which in the skeletal muscle the the a in the in in the in the a skeletal muscle in the muscle to the muscle to in the the to the muscle a in skeletal muscle the to in to in skeletal muscle to which the gene for a mice, a to in the in to mice, to a which the in the the the in in for to the for the for the the the in