Behavioral characterization of mice lacking the ubiquitin ligase UBR1 of the N-end rule pathway.

The N-end rule pathway, a subset of the ubiquitin pathway, relates the in vivo half-life of a protein to the identity of its N-terminal residue. Mice lacking NTAN1, a component of the N-end rule pathway, showed altered learning and memory, and socially conditioned behavioral alteration (Balogh, Kwon, & Denenberg 1999, 2000; Kwon, Balogh et al. 2000; Balogh et al. 2001). Mice lacking UBR1 (E3alpha), one of at least three recognition components of the N-end rule pathway, are viable and outwardly normal. Here we describe behavioral characterizations of UBR1 knockout (UBR1-/-) mice. Compared to congenic littermates, UBR1-/- mice exhibited less spontaneous activity in an open field and took longer to locate the hidden platform during eight-week Morris water maze retention. In contrast, they performed better in horizontal-vertical discrimination and Lashley III maze testing. No statistically significant differences in inhibitory learning were observed. With the exception of enhanced Lashley III maze performance, these data parallel findings with NTAN1-/- mice lacking the upstream component of UBR1. These results suggest that, like NTAN1, UBR1 is involved in learning and memory.