Effects of Na+-Ca2+ exchange expression on excitation-contraction coupling in genetically modified mice. 2005

Joshua I Goldhaber, and Scott A Henderson, and Hannes Reuter, and Christian Pott, and Kenneth D Philipson
Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. jgoldhaber@mednet.ucla.edu

We have created genetically altered mice to investigate how expression of the Na(+)-Ca(2+) exchange protein alters excitation-contraction (E-C) coupling. Whereas low levels of exchanger overexpression have minimal effects on E-C coupling properties, high levels of overexpression in homozygous animals results in susceptibility to hypertrophy and heart failure, along with a significant reduction in E-C coupling gain. While global knockout of the exchanger in mice is embryonic-lethal, conditional knockout mice live to adulthood. Cardiac function is surprisingly normal in seven-week-old mice, but E-C coupling gain is apparently increased. Thus, genetic modification of exchanger expression has a major influence on E-C coupling.

UI MeSH Term Description Entries
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D006332 Cardiomegaly Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES. Cardiac Hypertrophy,Enlarged Heart,Heart Hypertrophy,Heart Enlargement,Cardiac Hypertrophies,Enlargement, Heart,Heart Hypertrophies,Heart, Enlarged,Hypertrophies, Cardiac,Hypertrophies, Heart,Hypertrophy, Cardiac,Hypertrophy, Heart
D006720 Homozygote An individual in which both alleles at a given locus are identical. Homozygotes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D019831 Sodium-Calcium Exchanger An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart. Ca(2+)-Na(+) Exchanger,Calcium-Sodium Carrier,Calcium-Sodium Exchanger,Na(+)-Ca(2+) Exchanger,Sodium-Calcium Carrier,Ca(2+)-Na(+) Antiporter,Calcium-Sodium Antiporter,Na(+)-Ca(2+) Antiporter,Sodium-Calcium Antiporter,Antiporter, Calcium-Sodium,Antiporter, Sodium-Calcium,Calcium Sodium Antiporter,Calcium Sodium Carrier,Calcium Sodium Exchanger,Carrier, Calcium-Sodium,Carrier, Sodium-Calcium,Exchanger, Calcium-Sodium,Exchanger, Sodium-Calcium,Sodium Calcium Antiporter,Sodium Calcium Carrier,Sodium Calcium Exchanger
D020022 Genetic Predisposition to Disease A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. Genetic Predisposition,Genetic Susceptibility,Predisposition, Genetic,Susceptibility, Genetic,Genetic Predispositions,Genetic Susceptibilities,Predispositions, Genetic,Susceptibilities, Genetic

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