Yt. Kwon et al., Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway, MOL CELL B, 20(11), 2000, pp. 4135-4148
The N-end rule relates the in vivo half-life of a protein to the identity o
f its N-terminal residue. N-terminal asparagine and glutamine are tertiary
destabilizing residues, in that they are enzymatically deamidated to yield
secondary destabilizing residues aspartate and glutamate, which are conjuga
ted to arginine, a primary destabilizing residue. N-terminal arginine of a
substrate protein is bound by the Ubr1-encoded E3 alpha, the E3 component o
f the ubiquitin-proteasome-dependent N-end rule pathway. We describe the co
nstruction and analysis of mouse strains lacking the asparagine-specific N-
terminal amidase (Nt(N)-amidase), encoded by the Ntan1 gene. In wild-type e
mbryos, Ntan1 was strongly expressed in the branchial arches and in the tai
l and limb buds. The Ntan1(-/-) mouse strains lacked the Nt(N)-amidase acti
vity but retained glutamine-specific Nt(Q)-amidase, indicating that the two
enzymes are encoded by different genes. Among the normally short-lived N-e
nd rule substrates, only those bearing N-terminal asparagine became long-li
ved in Ntan1(-/-) fibroblasts,;The Ntan1(-/-) mice were fertile and outward
ly normal but differed from their congenic wild-type counterparts in sponta
neous activity, spatial memory, and a socially conditioned exploratory phen
otype that has not been previously described with other mouse strains.