Transgenic mouse models for cardiac dysfunction by a specific gene manipulation.
The sarcoplasmic reticulum Ca2+ ATPase (SERCA) plays a pivotal role in calcium cycling and the beat-to-beat function of the heart. Recent studies have shown that decreased expression and activity of SERCA are associated with end-stage heart failure in humans and in experimental animal models of heart failure. There has been considerable controversy over whether a decrease in SERCA level is a cause or effect of hypertrophy. To address directly whether alterations in SERCA levels modify calcium homeostasis and heart function, we have chosen to alter the SERCA protein expression genetically using transgenic and gene-targeted knockout mouse technology. This chapter describes the methodology for generation of mouse models that overexpress different SERCA isoforms and a SERCA2 knockout mouse model with decreased SERCA levels.
Babu
Gopal J
GJ
Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA.
Periasamy
Muthu
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D011401:Promoter Regions, Genetic; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D007527:Isoenzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; C506947:Atp2a2 protein, mouse; D000252:Calcium-Transporting ATPases; D002118:Calcium