page_title: Major urinary proteins
section_title: Pheromones
hierarchical_section_title: Major urinary proteins / Function / Pheromones
caption_attribution_description: English: A 18,956 Da major urinary protein identified by gel electrophoresis. Urine pooled from five C57BL/6J males and five females was resolved by non-denaturing (native) electrophoresis. The specific band indicated by the arrow, Mup25, is exclusively in male urine, and the total abundance of Mup protein is much higher in males than females. The image is modified from Figure 6A from the source.
context_page_description: Major urinary proteins, also known as α₂u-globulins, are a subfamily of proteins found in abundance in the urine and other secretions of many animals. Mups provide a small range of identifying information about the donor animal, when detected by the vomeronasal organ of the receiving animal. They belong to a larger family of proteins known as lipocalins. Mups are encoded by a cluster of genes, located adjacent to each other on a single stretch of DNA, that varies greatly in number between species: from at least 21 functional genes in mice to none in humans. Mup proteins form a characteristic glove shape, encompassing a ligand-binding pocket that accommodates specific small organic chemicals.
  Urinary proteins were first reported in rodents in 1932, during studies by Thomas Addis into the cause of proteinuria. They are potent human allergens and are largely responsible for a number of animal allergies, including to cats, horses and rodents. Their endogenous function within an animal is unknown but may involve regulating energy expenditure.
context_section_description: Studies have sought to find the precise function of Mups in pheromone communication. Mup proteins have been shown to promote puberty and accelerate the estrus cycle in female mice, inducing the Vandenbergh and Whitten effects. However, in both cases the Mups had to be presented to the female dissolved in male urine, indicating that the protein requires some urinary context to function. In 2007 Mups normally found in male mouse urine were made in transgenic bacteria, and therefore created devoid of the chemicals they normally bind. These Mups were shown to be sufficient to promote aggressive behaviour in males, even in the absence of urine. In addition, Mups made in bacteria were found to activate olfactory sensory neurons in the vomeronasal organ (VNO), a subsystem of the nose known to detect pheromones via specific sensory receptors, of mice and rats. Together, this demonstrated that Mup proteins can act as pheromones themselves, independent of their ligands.
  Consistent with a role in male-male aggression, adult male mice secrete significantly more Mups into their urine than females, juveniles or castrated male mice. The precise mechanism driving this difference between the sexes is complex, but at least three hormones—testosterone, growth hormone and thyroxine—are known to positively influence the production of Mups in mice. Wild house mouse urine contains variable combinations of four to seven distinct Mup proteins per mouse. Some inbred laboratory mouse strains, such as BALB/c and C57BL/6, also have different proteins expressed in their urine. However, unlike wild mice, different individuals from the same strain express the same protein pattern, an artifact of many generations of inbreeding. One unusual Mup is less variable than the others: it is consistently produced by a high proportion of wild male mice and is almost never found in female urine. When this Mup was made in bacteria and used in behavioural testing, it was found to attract female mice. Other Mups were tested but did not have the same attractive qualities, suggesting the male-specific Mup acts as a sex pheromone. Scientists named this Mup darcin (Mup20, Q5FW60) as a humorous reference to Fitzwilliam Darcy, the romantic hero from Pride and Prejudice. Taken together, the complex patterns of Mups produced has the potential to provide a range of information about the donor animal, such as gender, fertility, social dominance, age, genetic diversity or kinship. Wild mice (unlike laboratory mice that are genetically identical and which therefore also have identical patterns of Mups in the urine) have individual patterns of Mup expression in their urine that act as a "barcode" to uniquely identify the owner of a scent mark.
  In the house mouse, the major MUP gene cluster provides a highly polymorphic scent signal of genetic identity.  Wild mice breeding freely in semi-natural enclosures showed inbreeding avoidance.  This avoidance resulted from a strong deficit in successful matings between mice sharing both MUP haplotypes (complete match). In another study, using white-footed mice, it was found that when mice derived from wild populations were inbred, there was reduced survival when such mice were reintroduced into a natural habitat.  These findings suggest that inbreeding reduces fitness, and that scent signal recognition has evolved in mice as a means of avoiding inbreeding depression.
caption: The Mups in C57BL/6J mouse urine analyzed by native gel electrophoresis
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