%0 Journal Article %1 Peri_1999_2556 %A Periasamy, M. %A Reed, T. D. %A Liu, L. H. %A Ji, Y. %A Loukianov, E. %A Paul, R. J. %A Nieman, M. L. %A Riddle, T. %A Duffy, J. J. %A Doetschman, T. %A Lorenz, J. N. %A Shull, G. E. %D 1999 %J J. Biol. Chem. %K 9891028 ATPase, Animals, Base Calcium, DNA Female, Gov't, Heart, Heterozygote, Isoenzymes, Male, Messenger, Mice, Mutant Mutation, P.H.S., Phenotype, Primers, RNA, Research Reticulum, Sarcoplasmic Sequence, Strains, Support, U.S. {C}a$^{2+}$-Transporting %N 4 %P 2556-62 %T Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca$^2+$-ATPase isoform 2 (SERCA2) gene. %U http://www.jbc.org/cgi/content/full/274/4/2556 %V 274 %X The sarco(endo)plasmic reticulum Ca$^2+$-ATPase isoform 2 (SERCA2) gene encodes both SERCA2a, the cardiac sarcoplasmic reticulum Ca$^2+$ pump, and SERCA2b, which is expressed in all tissues. To gain a better understanding of the physiological functions of SERCA2, we used gene targeting to develop a mouse in which the promoter and 5' end of the gene were eliminated. Mating of heterozygous mutant mice yielded wild-type and heterozygous offspring; homozygous mutants were not observed. RNase protection, Western blotting, and biochemical analysis of heart samples showed that SERCA2 mRNA was reduced by approximately 45\% in heterozygous mutant hearts and that SERCA2 protein and maximal velocity of Ca$^2+$ uptake into the sarcoplasmic reticulum were reduced by approximately 35\%. Measurements of cardiovascular performance via transducers in the left ventricle and right femoral artery of the anesthetized mouse revealed reductions in mean arterial pressure, systolic ventricular pressure, and the absolute values of both positive and negative dP/dt in heterozygous mutants. These results demonstrate that two functional copies of the SERCA2 gene are required to maintain normal levels of SERCA2 mRNA, protein, and Ca$^2+$ sequestering activity, and that the deficit in Ca$^2+$ sequestering activity due to the loss of one copy of the SERCA2 gene impairs cardiac contractility and relaxation.

@article{Peri_1999_2556, abstract = {The sarco(endo)plasmic reticulum {C}a$^{2+}$-ATPase isoform 2 (SERCA2) gene encodes both SERCA2a, the cardiac sarcoplasmic reticulum {C}a$^{2+}$ pump, and SERCA2b, which is expressed in all tissues. To gain a better understanding of the physiological functions of SERCA2, we used gene targeting to develop a mouse in which the promoter and 5' end of the gene were eliminated. Mating of heterozygous mutant mice yielded wild-type and heterozygous offspring; homozygous mutants were not observed. {RN}ase protection, Western blotting, and biochemical analysis of heart samples showed that SERCA2 m{RNA} was reduced by approximately 45\% in heterozygous mutant hearts and that SERCA2 protein and maximal velocity of {C}a$^{2+}$ uptake into the sarcoplasmic reticulum were reduced by approximately 35\%. Measurements of cardiovascular performance via transducers in the left ventricle and right femoral artery of the anesthetized mouse revealed reductions in mean arterial pressure, systolic ventricular pressure, and the absolute values of both positive and negative dP/dt in heterozygous mutants. These results demonstrate that two functional copies of the SERCA2 gene are required to maintain normal levels of SERCA2 m{RNA}, protein, and {C}a$^{2+}$ sequestering activity, and that the deficit in {C}a$^{2+}$ sequestering activity due to the loss of one copy of the SERCA2 gene impairs cardiac contractility and relaxation.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Periasamy, M. and Reed, T. D. and Liu, L. H. and Ji, Y. and Loukianov, E. and Paul, R. J. and Nieman, M. L. and Riddle, T. and Duffy, J. J. and Doetschman, T. and Lorenz, J. N. and Shull, G. E.}, biburl = {https://www.bibsonomy.org/bibtex/2df626cb6b128f83b010af4786b78f04b/hake}, description = {The whole bibliography file I use.}, file = {Peri_1999_2556.pdf:Peri_1999_2556.pdf:PDF}, interhash = {d9fa7e1437d6503933a628255fe072bd}, intrahash = {df626cb6b128f83b010af4786b78f04b}, journal = {J. Biol. Chem.}, key = 42, keywords = {9891028 ATPase, Animals, Base Calcium, DNA Female, Gov't, Heart, Heterozygote, Isoenzymes, Male, Messenger, Mice, Mutant Mutation, P.H.S., Phenotype, Primers, RNA, Research Reticulum, Sarcoplasmic Sequence, Strains, Support, U.S. {C}a$^{2+}$-Transporting}, month = Jan, number = 4, pages = {2556-62}, timestamp = {2009-06-03T11:21:25.000+0200}, title = {Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum {C}a$^{2+}$-ATPase isoform 2 (SERCA2) gene.}, url = {http://www.jbc.org/cgi/content/full/274/4/2556}, volume = 274, year = 1999 }