Abstract
ABSTRACTAmino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene,NAA10,encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants inNAA10. In mice,Naa10is not an essential gene, as there exists a paralogous gene,Naa12, that substantially rescuesNaa10knockout mice from embryonic lethality, whereas double knockouts (Naa10−/YNaa12−/−)are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of “maternal effect lethality” for heterozygousNaa10−/Xfemale mice, but we do observe a small amount of embryonic lethality in theNaa10−/ymale mice on the inbred genetic background in this different animal facility.
Publisher
Cold Spring Harbor Laboratory