Territorial Behavior and Social Stability in the Mouse Require Correct Expression of Imprinted Cdkn1c

Abstract

Genomic imprinting, the epigenetic process by which transcription occurs from a single parental allele, is believed to influence social behaviors in mammals. An important social behavior is group living, which is enriched in Eutherian mammals relative to monotremes and marsupials. Group living facilitates resource acquisition, defense of territory and co-care of young, but requires a stable social group with complex inter-individual relationships. Co-occurring with increased group living in Eutherians is an increase in the number of imprinted loci, including that spanning the maternally expressed Cdkn1c. Using a 'loss-of-imprinting' model of Cdkn1c (Cdkn1c^BACx1), we demonstrated that twofold over expression of Cdkn1c results in abnormal social behaviors. Although, our previous work indicated that male Cdkn1c^BACx1 mice were more dominant as measured by tube test encounters with unfamiliar wild-type (WT) males. Building upon this work, using more ecologically relevant assessments of social dominance, indicated that within their normal social group, Cdkn1c^BACx1 mice did not occupy higher ranking positions. Nevertheless, we find that presence of Cdkn1c^BACx1 animals within a group leads to instability of the normal social hierarchy, as indicated by greater variability in social rank within the group over time and an increase in territorial behavior in WT cage-mates. Consequently, these abnormal behaviors led to an increased incidence of fighting and wounding within the group. Taken together these data indicate that normal expression of Cdkn1c is required for maintaining stability of the social group and suggests that the acquisition of monoallelic expression of Cdkn1c may have enhanced social behavior in Eutherian mammals to facilitate group living.

Keywords: Cdkn1c (p57Kip2); dominance; epigenetics; genomic imprinting; social group.

FIGURE 1

Cdkn1c over expression does not affect dominance behaviors within the home cage group. There was no effect of GENOTYPE on the average group rank in the within-cage tube test (A), the scent marking task (B), and the water access task (C). Data shown are means ± SEM.

FIGURE 2

Presence of a Cdkn1c^BACx1 male destabilizes the established social hierarchy. In groups containing Cdkn1c^BACx1 males and their wild-type (WT) cage-mates there was no correlation between rank in the tube test and rank in the water access task in the first 120 s (A), nor rank in the scent marking task is correlated with rank in the water access task in 600 s (B). In cages of Cdkn1c^BACLacZ and their WT cage-mates, an animal’s rank in the tube test correlated with rank in the water access task in the first 120 s (C). Additionally, rank in the scent-marking task correlated with rank in the water access task in 600 s (D).

FIGURE 3

When odor cues indicating dominance are removed, Cdkn1c^BACx1 males change rank more frequently than WT. In groups of Cdkn1c^BACLacZ and WT animals, rank fluctuation did not differ when olfactory cues indicating the dominant animal were removed (A, left) nor when the environment remained stable (A, right). When odor cues were removed Cdkn1c^BACx1 males’ rank fluctuated significantly more than WT animals (B, left). This was not the case when the environment remained stable (B, right). Data shown are means ± SEM. ^∗p < 0.05.

FIGURE 4

Wild-type animals increased scent marking toward Cdkn1c^BACx1 but not Cdkn1c^BACLacZ animals. (A) There were greater levels of scent marking in Cdkn1c^BACx1 containing groups compared to Cdkn1c^BACLacZ containing groups. (B) WT cages mates of Cdkn1c^BACx1 animals scent marked more to transgenes (tg) than (C) WT cages mates of Cdkn1c^BACLacZ animals. Data shown are means ± SEM. ^&p = 0.07, ^∗p = 0.05.

FIGURE 5

Olfactory response to social and non-social odors is normal in Cdkn1c^BACx1 mice. There was no difference in time spent exploring a social odor (A). Latency to detect a non-social odor was similar between all groups (B).