Delayed embryonic development and impaired cell growth and survival in Actg1 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, β cytoand γ cyto -actin, are ubiquitously expressed. We found that γ cyto -actin null (Actg1 −/− ) mice were fully viable during embryonic development, but most died within 48 hours 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 γ 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 γ cyto -actin in cell growth and survival.

Biofabrication of a novel biomolecule-assisted reduced graphene oxide: an excellent biocompatible nanomaterial

“…Previous studies demonstrated that Actg1-/-MEFs were mildly growth impaired due to reduced cell survival. 82 Interestingly, NAM-rGO had no effect on the expression of cytoskeleton genes, whereas GO significantly reduced the expression level of Actr2, Actr3, Tuba1a, and Tuba1b. It indicated that GO resulted in a decrease in cell viability due to the downregulation of cytoskeleton genes.…”

Relative importance of βcyto- and γcyto-actin in primary mouse embryonic fibroblasts

“…γ cyto -Actin–null MEFs showed mild growth impairment and a small decrease in cell viability but were otherwise comparable to control cells in all other parameters tested (Bunnell and Ervasti, 2010; Bunnell et al , 2011). In contrast, β cyto -actin–knockout MEFs exhibited a wide range of more severe phenotypes (Bunnell et al , 2011).…”

Plant Vegetative and Animal Cytoplasmic Actins Share Functional Competence for Spatial Development with Protists

“…It would be interesting to see whether any of the vegetative plant actins or the ancestral protist actins can function in animals and suppress the embryo lethal phenotype of mice lacking ACTB (Shawlot et al, 1998;Bunnell et al, 2011) or the delayed embryonic development and poor survival of mice lacking ACTG1 (Bunnell and Ervasti, 2010). Moreover, because the human cytoplasmic actins are functional in Arabidopsis, missense mutations in these human actins that are associated with a large number of diseases, including blindness, deafness, myopathies, immune deficiency, and aberrant kidney function, could be easily tested in this plant model.…”