Аннотация
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.
- 9891028
- animals,
- atpase,
- base
- calcium,
- dna
- female,
- gov't,
- heart,
- heterozygote,
- isoenzymes,
- male,
- messenger,
- mice,
- mutant
- mutation,
- p.h.s.,
- phenotype,
- primers,
- research
- reticulum,
- rna,
- sarcoplasmic
- sequence,
- strains,
- support,
- u.s.
- {c}a$^{2+}$-transporting
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