Author:
Patrinostro Xiaobai,Roy Pallabi,Lindsay Angus,Chamberlain Christopher M.,Sundby Lauren J.,Starker Colby G.,Voytas Daniel F.,Ervasti James M.,Perrin Benjamin J.
Abstract
The highly similar cytoplasmic β- and γ-actins differ by only four functionally similar amino acids, yet previous in vitro and in vivo data suggest that they support unique functions due to striking phenotypic differences between Actb and Actg1 null mouse and cell models. To determine whether the four amino acid variances were responsible for the functional differences between cytoplasmic actins, we gene edited the endogenous mouse Actb locus to translate γ-actin protein. The resulting mice and primary embryonic fibroblasts completely lacked β-actin protein, but were viable and did not present with the most overt and severe cell and organismal phenotypes observed with gene knockout. Nonetheless, the edited mice exhibited progressive high-frequency hearing loss and degeneration of actin-based stereocilia as previously reported for hair cell-specific Actb knockout mice. Thus, β-actin protein is not required for general cellular functions, but is necessary to maintain auditory stereocilia.
Funder
HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases
HHS | NIH | National Institute on Deafness and Other Communication Disorders
Publisher
Proceedings of the National Academy of Sciences
Cited by
26 articles.
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