Essential nucleotide- and protein-dependent functions ofActb/β-actin

Significance Actin is required for many general and specialized cellular functions. Two isoforms, β-actin and γ-actin, are ubiquitously expressed and 99% identical in amino acid sequence, yet previous studies indicated only β-actin is indispensable for life. The nucleotide sequence of each gene also varies, providing additional regulation that may make β-actin indispensable. To separate the effects of protein and nucleotide sequences, the β-actin gene was edited to encode γ-actin protein, while retaining any regulation contained in the nucleotide sequence. The mice, which lack β-actin protein, are viable and appear to be normal. However, they develop progressive hearing loss as auditory sensory cells degenerate. Together, these results show that β-actin function depends on both its nucleotide and protein sequence.