Evaluating Possible Maternal Effect Lethality and Genetic Background Effects in Knockout Mice

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, , 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 in . In mice, is not an essential gene, as there exists a paralogous gene, , that substantially rescues knockout mice from embryonic lethality, whereas double knockouts ( Naa12 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 heterozygous female mice, but we do observe a small amount of embryonic lethality in the male mice on the inbred genetic background in this different animal facility.