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Evaluating possible maternal effect lethality of Naa10 knockout mice, and modulation of phenotypes for embryonic and neonatal lethality by genetic background and environment

Lyon, G.; Longo, J.; Garcia, A.; Inusa, F.; Marchi, E.; Shi, D.; Doerfel, M.; Arnesen, T.; Aldabe, R.; Lyons, S. K.; Nashat, M.; Bolton, D.

2023-04-27 genetics
10.1101/2023.04.27.538618 bioRxiv
Show abstract

Amino-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 in NAA10. In mice, Naa10 is not an essential gene, as there exists a paralogous gene, Naa12, that substantially rescues Naa10 knockout mice from embryonic lethality, whereas double knockouts (Naa10-/Y 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 Naa10-/X female mice, but we do observe a small amount of embryonic lethality in the Naa10-/ymale mice on the inbred genetic background in this different animal facility.

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