Protein pheromone MUP20/Darcin is a vector and target of indirect genetic effects in mice

Social behavior in animals is an adaptive process influenced by environmental factors and direct and indirect genetic effects. Indirect genetic effects (IGEs) include mechanisms by which individuals of particular genotypes can influence the behavioral phenotypes and genotypes (via modulated patterns of gene expression) of other individuals with different genotypes. In groups of adult mice, IGEs can be unidirectional, from one genotype to the other, or bidirectional, resulting in a homogenization of the behavioral phenotypes within the group. Critically, it has been theorized that IGEs constitute a large fitness target on which deleterious mutations can have pleiotropic effects, meaning that individuals carrying certain behavior-altering mutations can impose the fitness costs of those mutations on others comprising the broader social genome. Experimental data involving a mouse model support the existence of these IGE-amplified fitness losses; however, the underlying biological mechanisms that facilitate these remain unknown. In a mouse model of IGEs, we demonstrate that the Major Urinary Protein 20 pheromone, also called Darcin, produced by mice lacking the adhesion protein Neuroligin-3 acts as a vector to deleteriously modify the social behavior of wild-type mice. Additionally, we showed that lack of social interest on the part of Neuroligin-3 knockout mice is independent of their environment. These findings reveal a new role for mammalian pheromones in mediating the externalization of social deficits from one individual to others comprising the population through IGEs.Author SummaryIndirect genetic effects (IGEs) are mechanisms by which individuals of particular genotypes can influence the behavioral phenotype of individuals of different genotypes, sometimes disruptively, in instances where one member of the population carriers a deleterious behavior altering variant. Although disruptive IGEs have been demonstrated in mice, its underlying molecular and genetic mechanisms remain unknown. Using an IGEs mouse model, we demonstrated that the pheromone protein Major Urinary Protein 20, also named Darcin, is as a vector and target of social epistasis a specific type of IGEs. This finding reveals a new function for mammalian pheromones in mediating social epistasis to degrade group social behavior.

Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5-dihydrothiazole in female mice

The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the pups from pheromone-exposed dams exhibited enhanced learning. Sialic acid components in the milk are known to be involved in brain development. We hypothesized that the offspring might have received more of this key nutrient that promotes brain development. The mRNA for polysialyltransferase, which produces polysialylated neural cell adhesion molecules related to brain development, was increased in the brain of offspring of pheromone-exposed dams at post-natal day 10, while it was not different at embryonic stages, indicating possible differential brain development during early post-natal life.

Wesley Kingston Whitten 1918 - 2010

Wesley Kingston Whitten (1918?2010) was recognized as one of Australia's most innovative biological scientists. His studies were the precursor of the science of preimplantation embryology and the technology of assisted reproduction. He pioneered the study of mammalian pheromones and their receptor, the vomeronasal organ. He elucidated the genetic basis of hermaphroditism and mosaicism, and the timing and mechanism of X chromosome inactivation. Several of his recombinant mouse strains continue to provide models for a number of diseases.