MHC-associated and MHC-independent urinary chemosignals in mice

Eggert, Frank; Höller, Carsten; Luszyk, Dagmar; Müller-Ruchholtz, W; Ferstl, Roman

doi:10.1016/0031-9384(95)02029-2

Cited by 56 publications

(30 citation statements)

References 19 publications

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“…Instead it appears that differences in H-2 are signaled by different relative amounts of the components of a mixture of acids (for a contrasting view, see ref. 7), or what we have called compound odors (15). From our analysis we can speculate that this odortype mixture contains at least eight components (Table 2, P Ͻ 0.01).…”

Section: Discussionmentioning

confidence: 74%

“…Earlier attempts to apply this technique to the analysis of mouse urine suggested that there are distinguishable patterns of neutral volatile compounds in different H-2 haplotypes (6,7). However, these reported differences were not related to specific peaks in the chromatograms, which is necessary for the chemical characterization of the compounds involved in conveying odor information indicative of H-2 type.…”

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confidence: 99%

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Volatile signals of the major histocompatibility complex in male mouse urine

Singer

Beauchamp

Yamazaki

1997

Proc. Natl. Acad. Sci. U.S.A.

231

168

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Variation in the genes of the major histocompatibility complex (MHC) contributes to unique individual odors (odortypes) in mice, as demonstrated by the ability of trained mice in a Y-maze olfactometer to discriminate nearly identical inbred mice that differ genetically only at the MHC (MHC congenic mice), while they cannot distinguish genetically identical inbred mice. Similar distinctions are possible with urine, a substance that is involved in many facets of mouse chemical communication. This paper reports results supporting the hypothesis that the MHC-determined urinary odor is composed of a mixture of volatile carboxylic acids occurring in relative concentrations that are characteristic of the odortype. Y-maze behavioral testing of urine fractions from anion exchange chromatography indicates that volatile acids are necessary and sufficient to convey MHC odortype information. Diethyl ether extracts, which are expected to contain the more volatile, less polar organic acids, were also discriminable in the Y-maze olfactometer. Ether extracts of 12 different urine samples from each of two panels of MHC congenic mice were analyzed by gas chromatography. No compounds unique to urine of either genotype were detected, but compounds did appear to occur in characteristic ratios in most of the samples of each type. Nonparametric statistical analysis of the gas chromatographic data showed that eight of the peaks occurred in significantly different relative concentrations in the congenic samples. One of the peaks was shown to represent phenylacetic acid, which has implications for the mechanism of the MHC specification of odortype.

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Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

Volatile signals of the major histocompatibility complex in male mouse urine

Singer

Beauchamp

Yamazaki

1997

Proc. Natl. Acad. Sci. U.S.A.

231

168

View full text Add to dashboard Cite

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“…To evaluate this conjecture, several groups examined the urinary volatile profiles of MHC-congenic mice derived from different background strains (Eggert et al 1996;Willse et al 2006;Novotny et al 2007;Zomer et al 2009). Eggert et al (1996) investigated the urinary volatile metabolic profiles of BALB/c (H2 d ), BALB/k (H2 k ) and C3H (H2 k ) mice.…”

Section: Chemical Investigations Of Mhc Odourtype In Micementioning

confidence: 99%

“…Eggert et al (1996) investigated the urinary volatile metabolic profiles of BALB/c (H2 d ), BALB/k (H2 k ) and C3H (H2 k ) mice. Unlike virtually all other studies to date, where almost all components were detected in the mouse urines, only 36 out of 55 peaks were found to be present in all three strains.…”

Section: Chemical Investigations Of Mhc Odourtype In Micementioning

confidence: 99%

In search of the chemical basis for MHC odourtypes

et al. 2010

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Mice can discriminate between chemosignals of individuals based solely on genetic differences confined to the major histocompatibility complex (MHC). Two different sets of compounds have been suggested: volatile compounds and non-volatile peptides. Here, we focus on volatiles and review a number of publications that have identified MHC-regulated compounds in inbred laboratory mice. Surprisingly, there is little agreement among different studies as to the identity of these compounds. One recent approach to specifying MHC-regulated compounds is to study volatile urinary profiles in mouse strains with varying MHC types, genetic backgrounds and different diets. An unexpected finding from these studies is that the concentrations of numerous compounds are influenced by interactions among these variables. As a result, only a few compounds can be identified that are consistently regulated by MHC variation alone. Nevertheless, since trained animals are readily able to discriminate the MHC differences, it is apparent that chemical studies are somehow missing important information underlying mouse recognition of MHC odourtypes. To make progress in this area, we propose a focus on the search for behaviourally relevant odourants rather than a random search for volatiles that are regulated by MHC variation. Furthermore, there is a need to consider a 'combinatorial odour recognition' code whereby patterns of volatile metabolites (the basis for odours) specify MHC odourtypes.

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“…21). Volatile odorants, as well as degraded MHC molecules and peptides, appear in the urine and bodily fluids of vertebrates and may thus facilitate odor detection (22)(23)(24). If genetic variation at these candidate loci imparts relevant olfactory information, this would provide the mechanistic basis for MHC-disassortative mating preferences.…”

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confidence: 99%

Discrimination of MHC-derived odors by untrained mice is consistent with divergence in peptide-binding region residues

Carroll

Penn

Potts

2002

Proc. Natl. Acad. Sci. U.S.A.

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Genes of the major histocompatibility complex (MHC) play a central role in immune recognition, yet they also influence the odor of individuals. Mice can be trained to distinguish odors mediated by classical MHC loci; however, training can introduce confounding behavioral artifacts. This study demonstrates that mice can distinguish some, but not all, naturally occurring allelic variants at classical MHC loci without prior training. This result suggests that MHC-disassortative mating preferences might operate by means of small MHC-based odor differences, and could therefore contribute to diversifying selection acting on MHC loci. Here we show that odors of two MHC mutant mouse strains (bm1 and bm3) can be distinguished, even after genetic background is controlled by intercrossing strains. These two strains differ by five amino acids, three of which are predicted to chemically contact peptides bound to the peptide-binding region (PBR), the site of antigen presentation for T cell recognition. However, the odors of neither bm1 nor bm3 were distinguished from their parental B6 haplotype after randomizing genomic background, despite discrimination of purebred B6 and bm1 strain odors. These combined results suggest that (i) there may be an MHC odor discrimination threshold based on divergence in PBR residues, providing a more logical pattern of MHC-based odor discrimination than found in previous training studies, where discrimination ability was not correlated with PBR divergence; and (ii) additional (non-MHC) mutations that influence odor have accumulated in these strains during the 100 generations of divergence between pure B6 and bm1 strains.

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MHC-associated and MHC-independent urinary chemosignals in mice

Cited by 56 publications

References 19 publications

Volatile signals of the major histocompatibility complex in male mouse urine

Volatile signals of the major histocompatibility complex in male mouse urine

In search of the chemical basis for MHC odourtypes

Discrimination of MHC-derived odors by untrained mice is consistent with divergence in peptide-binding region residues

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