Delayed embryonic development and impaired cell growth and survival in <i>Actg1</i> null mice

Abstract

Actins are among the most highly expressed proteins in eukaryotes and play a central role in nearly all aspects of cell biology. While the intricate process of development undoubtedly requires a properly regulated actin cytoskeleton, little is known about the contributions of different actin isoforms during embryogenesis. Of the six actin isoforms, only the two cytoplasmic actins, beta(cyto)- and gamma(cyto)-actin, are ubiquitously expressed. We found that gamma(cyto)-actin null (Actg1(-/-)) mice were fully viable during embryonic development, but most died within 48 h of birth due to respiratory failure and cannibalization by the parents. While no morphogenetic defects were identified, Actg1(-/-) mice exhibited stunted growth during embryonic and postnatal development as well as delayed cardiac outflow tract formation that resolved by birth. Using primary mouse embryonic fibroblasts, we confirm that gamma(cyto)-actin is not required for cell migration. The Actg1(-/-) cells, however, exhibited growth impairment and reduced cell viability, defects which perhaps contribute to the stunted growth and developmental delays observed in Actg1(-/-) embryos. Since the total amount of actin protein was maintained in Actg1(-/-) cells, our data suggests a distinct requirement for gamma(cyto)-actin in cell growth and survival.