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Basic science: Cardiovascular disease basic research
e0088 Mouse model carrying LMNAE82K mutation in myocardium develops dilated cardiomyopathy and apoptosis
  1. Lu Dan,
  2. Lian Hong,
  3. Shao Haitao,
  4. Quan Xiongzhi,
  5. Huang Lan,
  6. Zhang Lianfeng
  1. Institute of Laboratory Animal Science Chinese Academy of Medical Science


Objective To analyse the effects of LMNAE82K mutation on the transgenic mice heart.

Methods The transgenic mice were created by microinjection. Pathological changes in the heart of transgenic mice were observed by analyses from histologic, transmission electron microscopic, echocardiographic and ECG measurements. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), Col3α1, lamin A/C, emerin, fas, caspase-3, caspase-8, caspase-9 and cytochrome c in the myocardium of transgenic mice were determined by Reverse transcription PCR, Western Blot or immunofluorescence. Apoptiotic cells were detected by In situ terminal dUTP nick end-labelling (TUNEL) analyses.

Results Two lines, indicating cardiac-specific over-expression of h-LMNAE82K, were established amongst the transgenic mice. All the changes of the LMNAE82K transgenic mice heart displayed a similar pathological phenotype to dilated cardiomyopathy. To sum up, the LMNAE82K hearts exhibit thin-walled, dilated left and right ventricles, and had increased heart to body weight ratios as compared to WT hearts. Interstitial fibrosis, slight disarray of myofibrils, swollen mitochondria and loss of cristae as well as the loss of nuclear envelope integrity were observed in the myocardium of the LMNAE82K transgenic mice. The expression of fetal gene, BNP, was elevated in the LMNAE82K transgenic mice. Apoptosis in myocytes of LMNAE82K transgenic mice was detectable by TUNEL assay, apoptosis-related molecular signalling, especially in the Fas pathway, were activated by using Western Blot and immunofluorescence analysis.

Conclusions LMNAE82K transgenic mice developed DCM similar to the clinical features of human laminopathies and the most noteworthy was the apoptosis mechanism found in this transgenic mice. It may be a regulatory pathway providing an attractive therapeutic for the treatment of cardiomyopathy.

  • Dilated cardiomyopathy
  • lamin A/C gene
  • mutation
  • apoptosis
  • transgenic mice

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