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October 26, 2001Circulation Research

Replacement of the Muscle-Specific Sarcoplasmic Reticulum Ca 2+ -ATPase Isoform SERCA2a by the Nonmuscle SERCA2b Homologue Causes Mild Concentric Hypertrophy and Impairs Contraction-Relaxation of the Heart

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Key result

Replacing SERCA2a with SERCA2b in mice increases early mortality by ~20% and impairs cardiac contraction.

Why the study?

The requirement of muscle-specific SERCA2a isoform for normal cardiac function and development was unclear.

Population

Homozygous SERCA2a(-/-) mice with disrupted SERCA2a splicing mechanism

Comparison

Replacement of SERCA2a by SERCA2b isoform versus wild-type mice

Design

Gene targeting preclinical study in mice

Authors

MHMark Ver HeyenSHStéphane HeymansGAGudrun Antoons

Discussion

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Overview

SERCA2a isoform specificity is essential in cardiac muscle; leaves open whether selective modulation offers therapeutic benefit in human HF.

Structured PICO

P
Population
Mice with targeted disruption of the SERCA2a splicing mechanism (homozygous SERCA2a(-/-) mice)
I
Intervention
Replacement of the muscle-specific SERCA2a isoform by the nonmuscle SERCA2b homologue via gene targeting
C
Comparator
Wild-type mice and mice expressing similar cardiac levels of SERCA2a
O
Outcome
Cardiac development, morphology, and contraction-relaxation functionsurrogate

The muscle-specific SERCA2a isoform is essential for normal cardiac development and the contraction-relaxation cycle, as its replacement by SERCA2b leads to hypertrophy and impaired cardiac function.

Cite This Study

Heyen et al. (2001) studied Cardiac function and development. SERCA2a gene disruption (SERCA2a(-/-)) vs. Wild-type mice was evaluated on Cardiac function, mortality, and morphology. Replacement of the muscle-specific SERCA2a isoform by SERCA2b in mice caused a ~20% increase in early mortality, mild concentric cardiac hypertrophy, and impaired contraction-relaxation.

synapsesocial.com/papers/6aa91cd2d6272436db5aca4bhttps://doi.org/10.1161/hh2101.098466
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Overexpression of SERCA2b in the Heart Leads to an Increase in Sarcoplasmic Reticulum Calcium Transport Function and Increased Cardiac Contractility2000 · 67 citations
  2. 2Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation.1997 · 325 citations
  3. 3Targeted Overexpression of the Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Increases Cardiac Contractility in Transgenic Mouse Hearts1998 · 214 citations
  4. 4Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) gene products are regulated post-transcriptionally during rat cardiac development1999 · 28 citations
  5. 5The functional importance of the extreme C-terminal tail in the gene 2 organellar Ca2+-transport ATPase (SERCA2a/b)1994 · 84 citations