The interplay between urinary meprin and chemical signalling in the house mouse

House mice, Mus musculus domesticus, must communicate effectively to conspecifics within nocturnal, often densely vegetated environments, a lifestyle adopted in retaliation to predation risk. As such, mice have adapted by evolving a highly specialised method of communication via scent, the major vector of which being urine. Mice purposely deposit urine around their environment, a strategy known as scent marking. The urine of rodents contains both volatile and involatile chemical cues that convey an array of information regarding the scent owner, which the receiving mouse can utilise in subsequent social and mate choices. Alongside scent components which relay information, on the current status of the scent owner, fixed genetically determined components advertise scent mark ownership, enabling linkage of the information gathered from a scent to the scent owner, important should the receiver and signaller ever physically meet. House mice achieve such a genetically determined signal of individuality within urine by expression of an obligate proteinurea, 99% of which is attributable to the polymorphic major urinary proteins (MUPs). Such protein urea is a specific characteristic of rodents. An array of MUP isoforms are expressed within the urine of an individual house mouse, such that unrelated individuals within wild populations are unlikely to share the same MUP profile. In addition to providing a signal of identity, MUP profile is also used as a signal of genetic heterozygosity and in the avoidance of inbreeding. MUPS additionally function to bind and prolong the release of volatile urinary components, increasing the period of scent advertisement within the environment. A second group of genetically determined chemicals, suggested to be present within the urine of mice, are the major histocompatibility complex (MHC) class 1 peptide ligands, products of proteosomal degradation of self and non-self intracellular proteins. The sequences of such peptides displayed on the MHC molecules of cells and therefore excreted within urine are under the constraints of the MHC haplotype of the individual, and are therefore implicated in the signalling of genetic identity. Given the abundance of functional proteins and possibly peptides in the urine of mice it is intriguing that high levels of the soluble protease, meprin, are also observed, again a characteristic unique among rodents. Could urinary meprin in some way be involved in the manifestation of protein and peptide based cues? The pattern of urinary rneprin expression in wild populations of house mice is unknown; however inbred strains display polymorphism in urinary meprin phenotype. If meprin acts in the alteration of urinary cues, heterogeneity in urinary meprin expression may be maintained in wild populations, offering a new dimension of scent polymorphism, independent of the genes under which such cues are encoded or constrained. In this investigation the prevalence and abundance of urinary meprin within wild derived house mice was assessed. Most mice sampled had detectable levels of rneprin within their urine, consistent with urinary meprin expression conferring a selective advantage in wild populations. A wide range of urinary meprin abundance levels were observed and males expressed urinary meprin in greater abundance than females, indicating that urinary meprin levels are under regulatory control. To determine if the prevalence and abundance of urinary meprin observed was reflective of a role in chemical communication, the activity of meprin towards both MUPs and MHC class I peptide ligands within urine was investigated. Whilst MUPs remained stable, MHC peptide ligands were unable to persist within the urine of house mice. The data indicated that urinary meprin contributed to, but was not solely responsible for, such instability. Given the similarities in the mechanism of MHC ligand detection between the chemosensory and immune systems, it is suggested that urinary meprin function is linked to the immune response, consistent with the location of the rneprin gene on chromosome 17. The activity of urinary meprin towards MHC pep tides may serve to destroy a signal of disease status to conspecifics. This does not likely explain the sexual dimorphism observed however, indicating additional functions of urinary rneprin, ideas of which, and future work to investigate, are discussed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo