Cellular Disorganization and Extensive Apoptosis in the Developing Heart of Mice that Lack Cardiac Muscle α-Actin: Apparent Cause of Perinatal Death

Eltyeb Abdelwahid*, Lauri J. Pelliniemi, John C. Szucsik, James L. Lessard, Eero Jokinen

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Mice that lack cardiac muscle α-actin die during the perinatal period. Approximately 56% of mice that are homozygous null (-/-) for a functional cardiac α-actin gene do not survive to term, and the remainder generally die within 2 wk of birth. We found that there were neither morphologic differences nor differences in the extent of apoptosis between the mutant and normal hearts on embryonic day (E) 12 and E14 of development. However, apoptosis was greater in the hearts of homozygous null mice on E17 and postnatal day 1 when compared with wild-type hearts. The antiapoptotic factor Bcl-x/L was localized in regions adjacent to where apoptosis was detected. The distribution patterns of the apoptosis triggering protein p53 were similar to those of apoptotic cells. The growth of the prenatal and postnatal hearts of the cardiac α-actin-deficient mice was retarded, and the cytoplasmic filaments were disorganized. Although apoptotic cells were observed in both the atria and ventricles in the hearts of the homozygous null animals, the frequency was greater in the ventricles than in the atria. Our results indicate that the functional and structural disturbances in the mice with a homozygous lack of cardiac α-actin seem to be due to disorganized development of acto-myosin filaments in the affected cardiomyocytes. Other actin isoforms cannot compensate for the lack of cardiac α-actin, and this seems to induce apoptosis in defective cardiac myocytes, which are not able to cope with the increased workload in the perinatal phase.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalPediatric research
Volume55
Issue number2
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Fingerprint Dive into the research topics of 'Cellular Disorganization and Extensive Apoptosis in the Developing Heart of Mice that Lack Cardiac Muscle α-Actin: Apparent Cause of Perinatal Death'. Together they form a unique fingerprint.

  • Cite this