The Genetic Basis of Individual-Recognition Signals in the Mouse

Abstract

The major histocompatibility complex (MHC) is widely assumed to be a primary determinant of individual-recognition scents in many vertebrates [1-6], but there has been no functional test of this in animals with normal levels of genetic variation. Mice have evolved another polygenic and highly polymorphic set of proteins for scent communication, the major urinary proteins (MUPs) [7-12], which may provide a more reliable identity signature ([13, 14] and A.L. Sherborne, M.D.T., S. Paterson, F.J., W.E.R.O., P. Stockley, R.J.B., and J.L.H., unpublished data). We used female preference for males that countermark competitor male scents [15-17] to test the ability of wild-derived mice to recognize individual males differing in MHC or MUP type on a variable genetic background. Differences in MHC type were not used for individual recognition. Instead, recognition depended on a difference in MUP type, regardless of other genetic differences between individuals. Recognition also required scent contact, consistent with detection of involatile components through the vomeronasal system [6, 18]. Other differences in individual scent stimulated investigation but did not result in individual recognition. Contrary to untested assumptions of a vertebrate-wide mechanism based largely on MHC variation, mice use a species-specific [12] individual identity signature that can be recognized reliably despite the complex internal and external factors that influence scents [2]. Specific signals for genetic identity recognition in other species now need to be investigated.

In search of the chemical basis for MHC odourtypes

“…In this regard, there is as yet no direct evidence for the existence of MHC odourtypes in wild mice. Several studies have failed to find specific behavioural effects of MHC variation in wild mice (Cheetham et al 2007;Sherborne et al 2007;Thom et al 2008; but see Potts et al 1991). However, this cannot be taken as proof that they do not exist.…”

“…An atypical MUP that preferentially binds to 2-sec-butyl-4,5-dihydrothiazole is male-specific (Armstrong et al 2005). Variation in MUPs is extensive in wild populations, where they are involved in individual recognition (Hurst et al 2001;Cheetham et al 2007), inbreeding avoidance (Sherborne et al 2007) and evaluation of genetic heterozygosity of potential mates (Thom et al 2008). However, since large amounts of proteins are not generally observed in the urine of other mammals, including humans, MUP-like molecules probably have a more limited role in olfactory communication in those species.…”

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

“…It is now well established that, in freely behaving mice, nonvolatile peptides gain access to sensory neurons of both the main olfactory system and the VNO during behavioural situations involving direct physical contact 21,22 , that such peptides are powerful ligands for subsets of vomeronasal and olfactory sensory neurons [21][22][23][24][25] (VSNs and OSNs, respectively), that they induce brain activity downstream from the sensory neurons in vivo 26 , and that synthetic MHC peptide ligands can be discriminated in social preference tests 22 and influence social learning and reproductive function in the context of the Bruce effect test 21 . However, it is important to note that there is also considerable evidence for the use of MHC-independent, individual identity signatures in mice in specific behavioural contexts 27,28 (but see the discussion in Ruff et al 29 ).…”

Reintroducing domesticated wild mice to sociality induces adaptive transgenerational effects on MUP expression

“…Using a candidate-gene approach, we examine the major urinary proteins (MUPs), a primary component of urinary pheromones in mice. MUPs belong to a multigene family that conveys information about genetic identity and kin relatedness in wild mice (15,16). The quantitative role of MUP expression level also appears to have behavioral relevance: MUPs are expressed in high quantities in a sexually dimorphic fashion, with males expressing roughly four times that of females (17).…”