Major evolutionary transitions were always accompanied by genetic remodelling of phenotypic traits. For example, the vertebrate transition from water to land was accompanied by rapid evolution of olfactory receptors and by the expansion of genes encoding lipocalins, which - due to their transporting functions - represent an important interface between the external and internal organic world of an individual and also within an individual. Similarly, some lipocalin genes were lost along other genes when this transition went in the opposite direction leading, for example, to cetaceans. In terrestrial vertebrates, lipocalins are involved in the transport of lipophilic substances, chemical signalling, odour reception, antimicrobial defence and background odour clearance during ventilation. Many ancestral lipocalins have clear physiological functions across the vertebrate taxa while many other have - due to pleiotropic effects of their genes - multiple or complementary functions within the body homeostasis and development. The aim of this review is to deconstruct the physiological functions of lipocalins in light of current OMICs techniques. We concentrated on major findings in the house mouse in comparison to other model taxa (e.g., voles, humans, and birds) in which all or most coding genes within their genomes were repeatedly sequenced and their annotations are sufficiently informative.

Department of Zoology Faculty of Science Charles University BIOCEV Prague Czechia

Zobrazit více v PubMed

Abe T., Touhara K. (2014). Structure and function of a peptide pheromone family that stimulate the vomeronasal sensory system in mice. Biochem. Soc. Trans. 42, 873–877. doi: 10.1042/BST20140051, PMID: PubMed DOI

Abril J. F., Agarwal P., Alexandersson M., Antonarakis S. E., Baertsch R., Berry E., et al. . (2002). Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562. doi: 10.1038/nature01262, PMID: PubMed DOI

Ackels T., Erskine A., Dasgupta D., Marin A. C., Warner T. P. A., Tootoonian S., et al. . (2021). Fast odour dynamics are encoded in the olfactory system and guide behaviour. Nature 593, 558–563. doi: 10.1038/s41586-021-03514-2, PMID: PubMed DOI PMC

Álvarez M. D. G., Romero D. S., Greene L. H., Flower D. R. (2005). The lipocalin protein family: protein sequence, structure and relationship to the calycin superfamily. 17–27.

Bansal R., Nagel M., Stopkova R., Sofer Y., Kimchi T., Stopka P., et al. . (2021). Do all mice smell the same? Chemosensory cues from inbred and wild mouse strains elicit stereotypic sensory representations in the accessory olfactory bulb. BMC Biol. 19:133. doi: 10.1186/s12915-021-01064-7, PMID: PubMed DOI PMC

Belkaid Y., Harrison O. (2017). Homeostatic immunity and the microbiota. Immunity 46, 562–576. doi: 10.1016/j.immuni.2017.04.008, PMID: PubMed DOI PMC

Berghard A., Buck L. B. (1996). Sensory transduction in vomeronasal neurons: evidence for G alpha o, G alpha i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. J. Neurosci. 16, 909–918. doi: 10.1523/JNEUROSCI.16-03-00909.1996, PMID: PubMed DOI PMC

Bhatia S., Knoch B., Wong J., Kim W. S., Else P. L., Oakley A. J., et al. . (2012). Selective reduction of hydroperoxyeicosatetraenoic acids to their hydroxy derivatives by apolipoprotein D: implications for lipid antioxidant activity and Alzheimer’s disease. Biochem. J. 442, 713–721. doi: 10.1042/BJ20111166, PMID: PubMed DOI

Bianchi F., Flisi S., Careri M., Riboni N., Resimini S., Sala A., et al. . (2019). Vertebrate odorant binding proteins as antimicrobial humoral components of innate immunity for pathogenic microorganisms. PLoS One 14:e0213545. doi: 10.1371/journal.pone.0213545, PMID: PubMed DOI PMC

Bilkova B., Swiderska Z., Zita L., Laloe D., Charles M., Benes V., et al. . (2018). Domestic fowl breed variation in egg white protein expression: application of proteomics and transcriptomics. J. Agric. Food Chem. 66, 11854–11863. doi: 10.1021/acs.jafc.8b03099, PMID: PubMed DOI

Bímová B., Albrecht T., Macholán M., Piálek J. (2009). Signalling components of mate recognition system in the house mouse. Behav. Process. 80, 20–27. doi: 10.1016/j.beproc.2008.08.004, PMID: PubMed DOI

Bimova B. V., Macholan M., Baird S. J., Munclinger P., Dufkova P., Laukaitis C. M., et al. . (2011). Reinforcement selection acting on the European house mouse hybrid zone. Mol. Ecol. 20, 2403–2424. doi: 10.1111/j.1365-294X.2011.05106.x, PMID: PubMed DOI

Bingham R. J., Findlay J. B. C., Hsieh S. Y., Kalverda A. P., Kjellberg A., Chiara P., et al. . (2004). Thermodynamics of binding of 2-Methoxy-3-isopropylpyrazine and 2-Methoxy-3-isobutylpyrazine to the major urinary protein. J. Am. Chem. Soc. 126, 1675–1681. doi: 10.1021/ja038461i, PMID: PubMed DOI

Bishop R. E., Cambillau C., Prive G. G., Hsi D., Tillo D., Tillier E. R. M. (2006). “Bacterial lipocalins: origin, structure, and function,” in Lipocalins. eds. Akerstrom B., Borregaard N., Flower D. R., Salier J. P. (Georgetown, TX: Landes Bioscience; ), 28–40.

Brennan P. A., Kendrick K. M. (2006). Mammalian social odours: attraction and individual recognition. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 361, 2061–2078. doi: 10.1098/rstb.2006.1931, PMID: PubMed DOI PMC

Briand L., Blon F., Trotier D., Pernollet J.-C. (2004). Natural ligands of hamster aphrodisin. Chem. Senses 29, 425–430. doi: 10.1093/chemse/bjh044, PMID: PubMed DOI

Bryche B., Baly C., Meunier N. (2021). Modulation of olfactory signal detection in the olfactory epithelium: focus on the internal and external environment, and the emerging role of the immune system. Cell Tissue Res. 384, 589–605. doi: 10.1007/s00441-021-03467-y, PMID: PubMed DOI PMC

Bufe B., Zufall F. (2016). The sensing of bacteria: emerging principles for the detection of signal sequences by formyl peptide receptors. Biomol. Concepts 7, 205–214. doi: 10.1515/bmc-2016-0013, PMID: PubMed DOI

Byers S. L., Wiles M. V., Dunn S. L., Taft R. A. (2012). Mouse estrous cycle identification tool and images. PLoS One 7:e35538. doi: 10.1371/journal.pone.0035538, PMID: PubMed DOI PMC

Cann P., Chabi M., Delsart A., Le Danvic C., Saliou J.-M., Chasles M., et al. . (2019). The olfactory secretome varies according to season in female sheep and goat. BMC Genomics 20:794. doi: 10.1186/s12864-019-6194-z, PMID: PubMed DOI PMC

Carvalho V. M. A., Nakahara T. S., Cardozo L. M., Souza M. A. A., Camargo A. P., Trintinalia G. Z., et al. . (2015). Lack of spatial segregation in the representation of pheromones and kairomones in the mouse medial amygdala. Front. Neurosci. 9:283. doi: 10.3389/fnins.2015.00283, PMID: PubMed DOI PMC

Cavaggioni A., Sorbi R. T., Keen J. N., Pappin D. J. C., Findlay J. B. C. (1987). Homology between the pyrazine-binding protein form nasal mucosa and major urinary proteins. FEBS Lett. 212, 225–228. doi: 10.1016/0014-5793(87)81349-2, PMID: PubMed DOI

Cerna M., Kuntova B., Talacko P., Stopkova R., Stopka P. (2017). Differential regulation of vaginal lipocalins (OBP, MUP) during the estrous cycle of the house mouse. Sci. Rep. 7:11674. doi: 10.1038/s41598-017-12021-2, PMID: PubMed DOI PMC

Chamero P., Marton T. F., Logan D. W., Flanagan K., Cruz J. R., Saghatelian A., et al. . (2007). Identification of protein pheromones that promote aggressive behaviour. Nature 450, 899–903. doi: 10.1038/nature05997, PMID: PubMed DOI

Chang P. L., Kopania E., Keeble S., Sarver B. A. J., Larson E., Orth A., et al. . (2017). Whole exome sequencing of wild-derived inbred strains of mice improves power to link phenotype and genotype. Mamm. Genome 28, 416–425. doi: 10.1007/s00335-017-9704-9, PMID: PubMed DOI PMC

Charron J. B. F., Sarhan F. (2006). “Plant lipocalins,” in Lipocalins. eds. Akerstrom B., Borregaard N., Flower D. R., Salier J. P. (Georgetown, TX: Landes Bioscience; ), 41–48.

Cheetham S. A., Thom M. D., Jury F., Ollier W. E. R., Beynon R. J., Hurst J. L. (2007). The genetic basis of individual-recognition signals in the mouse. Curr. Biol. 17, 1771–1777. doi: 10.1016/j.cub.2007.10.007, PMID: PubMed DOI

Chu S. T., Lee Y. C., Nein K. M., Chen Y. H. (2000). Expression, immunolocalization and sperm-association of a protein derived from 24p3 gene in mouse epididymis. Mol. Reprod. Dev. 57, 26–36. doi: 10.1002/1098-2795(200009)57:1<26::AID-MRD5>3.0.CO;2-4, PMID: PubMed DOI

Clagett-Dame M., Knutson D. (2011). Vitamin A in reproduction and development. Nutrients 3, 385–428. doi: 10.3390/nu3040385, PMID: PubMed DOI PMC

Cora M. C., Kooistra L., Travlos G. (2015). Vaginal cytology of the laboratory rat and mouse: review and criteria for the staging of the estrous cycle using stained vaginal smears. Toxicol. Pathol. 43, 776–793. doi: 10.1177/0192623315570339, PMID: PubMed DOI PMC

Correnti C., Strong R. (2012). Mammalian siderophores, siderophore-binding lipocalins, and the labile iron pool. J. Biol. Chem. 287, 13524–13531. doi: 10.1074/jbc.R111.311829, PMID: PubMed DOI PMC

Costa S. L., Boekelheide K., Vanderhyden B. C., Seth R., Mcburney M. W. (1997). Male infertility caused by epididymal dysfunction in transgenic mice expressing a dominant negative mutation of retinoic acid receptor alpha 1. Biol. Reprod. 56, 985–990. doi: 10.1095/biolreprod56.4.985, PMID: PubMed DOI

Demir E., Li K., Bobrowski-Khoury N., Sanders J. I., Beynon R. J., Hurst J. L., et al. . (2020). The pheromone darcin drives a circuit for innate and reinforced behaviours. Nature 578, 137–141. doi: 10.1038/s41586-020-1967-8, PMID: PubMed DOI

Dey S., Chamero P., Pru J. K., Chien M.-S., Ibarra-Soria X., Spencer K. R., et al. . (2015). Cyclic regulation of sensory perception by a female hormone alters behavior. Cell 161, 1334–1344. doi: 10.1016/j.cell.2015.04.052, PMID: PubMed DOI PMC

Drickamer L. C. (2001). Urine marking and social dominance in male house mice (Mus musculus domesticus). Behav. Process. 53, 113–120. doi: 10.1016/S0376-6357(00)00152-2, PMID: PubMed DOI

Elangovan N., Lee Y. C., Tzeng W. F., Chu S. T. (2004). Delivery of ferric ion to mouse spermatozoa is mediated by lipocalin internalization. Biochem. Biophys. Res. Commun. 319, 1096–1104. doi: 10.1016/j.bbrc.2004.05.091, PMID: PubMed DOI

Enk V. M., Baumann C., Thoß M., Luzynski K. C., Razzazi-Fazeli E., Penn D. J. (2016). Regulation of highly homologous major urinary proteins in house mice quantified with label-free proteomic methods. Mol. BioSyst. 12, 3005–3016. doi: 10.1039/C6MB00278A, PMID: PubMed DOI PMC

Fischbach M., Lin H., Zhou L., Yu Y., Abergel R., Liu D., et al. . (2006). The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc. Natl. Acad. Sci. U. S. A. 103, 16502–16507. doi: 10.1073/pnas.0604636103, PMID: PubMed DOI PMC

Flo T. H., Smith K. D., Sato S., Rodriguez D. J., Holmes M. A., Strong R. K., et al. . (2004). Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917–921. doi: 10.1038/nature03104, PMID: PubMed DOI

Flower D. (1996). The lipocalin protein family: structure and function. Biochem. J. 318, 1–14. doi: 10.1042/bj3180001, PMID: PubMed DOI PMC

Fluckinger M., Haas H., Merschak P., Glasgow B., Redl B. (2004). Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores. Antimicrob. Agents Chemother. 48, 3367–3372. doi: 10.1128/AAC.48.9.3367-3372.2004, PMID: PubMed DOI PMC

Ganfornina M. D., Do Carmo S., Lora J. M., Torres-Schumann S., Vogel M., Allhorn M., et al. . (2008). Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 7, 506–515. doi: 10.1111/j.1474-9726.2008.00395.x, PMID: PubMed DOI PMC

Ganfornina M. D., Gutierrez G., Bastiani M., Sanchez D. (2000). A phylogenetic analysis of the lipocalin protein family. Mol. Biol. Evol. 17, 114–126. doi: 10.1093/oxfordjournals.molbev.a026224, PMID: PubMed DOI

Ganfornina M. D., Sánchez D., Bastiani M. J. (1995). Lazarillo, a new GPI-linked surface lipocalin, is restricted to a subset of neurons in the grasshopper embryo. Dev. Dent. 121, 123–134. PubMed

Ganfornina M. D., Sanchez D., Greene L. H., Flower D. R. (2006). “The lipocalin protein family: protein sequence, structure and relationship to the calycin superfamily,” in Lipocalins. eds. Akerstrom B., Borregaard N., Flower A. C. T., Salier J. P. (Georgetowns, TX: Landes Bioscience; ), 17–27.

Garénaux A., Houle S., Folch B., Dallaire G., Truesdell M., Lépine F., et al. . (2013). Avian lipocalin expression in chickens following Escherichia coli infection and inhibition of avian pathogenic Escherichia coli growth by ex-FABP. Vet. Immunol. Immunopathol. 152, 156–167. doi: 10.1016/j.vetimm.2012.09.018, PMID: PubMed DOI

Gerena R. L., Eguchi N., Urade Y., Killian G. J. (2000). Stage and region-specific localization of lipocalin-type prostaglandin D synthase in the adult murine testis and epididymis. J. Androl. 21, 848–854. PMID: PubMed

Goetz D., Holmes M., Borregaard N., Bluhm M., Raymond K., Strong R. (2002). The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell 10, 1033–1043. doi: 10.1016/S1097-2765(02)00708-6, PMID: PubMed DOI

Grolli S., Merli E., Conti V., Scaltriti E., Ramoni R. (2006). Odorant binding protein has the biochemical properties of a scavenger for 4-hydroxy-2-nonenal in mammalian nasal mucosa. FEBS J. 273, 5131–5514. doi: 10.1111/j.1742-4658.2006.05510.x, PMID: PubMed DOI

Grus W. E., Zhang J. (2008). Origin of the genetic components of the vomeronasal system in the common ancestor of all extant vertebrates. Mol. Biol. Evol. 26, 407–419. doi: 10.1093/molbev/msn262, PMID: PubMed DOI PMC

Guyonnet B., Zabet-Moghaddam M., Sanfrancisco S., Cornwall G. A. (2012). Isolation and proteomic characterization of the mouse sperm acrosomal matrix. Mol. Cell. Proteomics 11, 758–774. doi: 10.1074/mcp.M112.020339, PMID: PubMed DOI PMC

Haga S., Hattori T., Sato T., Sato K., Matsuda S., Kobayakawa R., et al. . (2010). The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor. Nature 466, 118–122. doi: 10.1038/nature09142, PMID: PubMed DOI

Hagemeyer P., Begall S., Janotova K., Todrank J., Heth G., Jedelsky P. L., et al. . (2011). Searching for major urinary proteins (MUPs) as chemosignals in urine of subterranean rodents. J. Chem. Ecol. 37, 687–694. doi: 10.1007/s10886-011-9971-y, PMID: PubMed DOI

Hamil K. G., Liu Q., Sivashanmugam P., Anbalagan M., Yenugu S., Soundararajan R., et al. . (2003). LCN6, a novel human epididymal lipocalin. Reprod. Biol. Endocrinol. 1:112. doi: 10.1186/1477-7827-1-112, PMID: PubMed DOI PMC

Hurst J. L., Gray S. J., Davey P., Young D., Corbishley J., Dawson C. (1997). Social interaction alters attraction to competitor's odour in the mouse Mus spretus Lataste. Anim. Behav. 54, 941–953. doi: 10.1006/anbe.1997.0515, PMID: PubMed DOI

Hurst J. L., Robertson D. H. L., Tolladay U., Beynon R. J. (1998). Proteins in urine scent marks of male house mice extend the longevity of olfactory signals. Anim. Behav. 55, 1289–1297. PubMed

Ibarra-Soria X., Levitin M. O., Logan D. W. (2014a). The genomic basis of vomeronasal-mediated behaviour. Mamm. Genome 25, 75–86. doi: 10.1007/s00335-013-9463-1, PMID: PubMed DOI PMC

Ibarra-Soria X., Levitin M. O., Saraiva L. R., Logan D. W. (2014b). The olfactory transcriptomes of mice. PLoS Genet. 10:e1004593. doi: 10.1371/journal.pgen.1004593, PMID: PubMed DOI PMC

Ibarra-Soria X., Nakahara T. S., Lilue J., Jiang Y., Trimmer C., Souza M. A., et al. . (2017). Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated. elife 6:e21476. doi: 10.7554/eLife.21476, PMID: PubMed DOI PMC

Janotova K., Stopka P. (2011). The level of major urinary proteins is socially regulated in wild Mus musculus musculus. J. Chem. Ecol. 37, 647–656. doi: 10.1007/s10886-011-9966-8, PMID: PubMed DOI

Jauregui E. J., Mitchell D., Topping T., Hogarth C. A., Griswold M. D. (2018). Retinoic acid receptor signaling is necessary in steroidogenic cells for normal spermatogenesis and epididymal function. Development 145:dev160465. doi: 10.1242/dev.160465, PMID: PubMed DOI PMC

Johnson E., Srikanth C., Sandgren A., Harrington L., Trebicka E., Wang L., et al. . (2010). Siderocalin inhibits the intracellular replication of mycobacterium tuberculosis in macrophages. FEMS Immunol. Med. Microbiol. 58, 138–145. doi: 10.1111/j.1574-695X.2009.00622.x, PMID: PubMed DOI PMC

Julien L., Baron F., Bonnassie S., Nau F., Guerin C., Jan S., et al. . (2019). The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against salmonella. Biometals 32, 453–467. doi: 10.1007/s10534-019-00180-w, PMID: PubMed DOI PMC

Kaur A. W., Ackels T., Kuo T. H., Cichy A., Dey S., Hays C., et al. . (2014). Murine pheromone proteins constitute a context-dependent combinatorial code governing multiple social behaviors. Cell 157, 676–688. doi: 10.1016/j.cell.2014.02.025, PMID: PubMed DOI PMC

Kido T., Arata S., Suzuki R., Hosono T., Nakanishi Y., Miyazaki J., et al. . (2005). The testicular fatty acid binding protein PERF15 regulates the fate of germ cells in PERF15 transgenic mice. Develop. Growth Differ. 47, 15–24. doi: 10.1111/j.1440-169x.2004.00775.x, PMID: PubMed DOI

Koskinen K., Reichert J., Hoier S., Schachenreiter J., Duller S., Moissl-Eichinger C., et al. . (2018). The nasal microbiome mirrors and potentially shapes olfactory function. Sci. Rep. 8:1296. doi: 10.1038/s41598-018-19438-3, PMID: PubMed DOI PMC

Kuntova B., Stopkova R., Stopka P. (2018). Transcriptomic and proteomic profiling revealed high proportions of odorant binding and antimicrobial defense proteins in olfactory tissues of the house mouse. Front. Genet. 9:26. doi: 10.3389/fgene.2018.00026, PMID: PubMed DOI PMC

Kwak J., Grigsby C. C., Preti G., Rizki M. M., Yamazaki K., Beauchamp G. K. (2013). Changes in volatile compounds of mouse urine as it ages: their interactions with water and urinary proteins. Physiol. Behav. 120, 211–219. doi: 10.1016/j.physbeh.2013.08.011, PMID: PubMed DOI

Kwak J., Grigsby C. C., Rizki M. M., Preti G., Koksal M., Josue J., et al. . (2012). Differential binding between volatile ligands and major urinary proteins due to genetic variation in mice. Physiol. Behav. 107, 112–120. doi: 10.1016/j.physbeh.2012.06.008, PMID: PubMed DOI

Kwak J., Josue J., Faranda A., Opiekun M. C., Preti G., Osada K., et al. . (2011). Butylated hydroxytoluene is a ligand of urinary proteins derived from female mice. Chem. Senses 36, 443–452. doi: 10.1093/chemse/bjr015, PMID: PubMed DOI

Kwak J., Strasser E., Luzynski K., Thoß M., Penn D. J. (2016). Are MUPs a toxic waste disposal system? PLoS One 11:e0151474. doi: 10.1371/journal.pone.0151474, PMID: PubMed DOI PMC

Lacazette E., Gachon A., Pitiot G. (2000). A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: differential expression in the oral and genital spheres. Hum. Mol. Genet. 9, 289–301. doi: 10.1093/hmg/9.2.289, PMID: PubMed DOI

Lareyre J. J., Winfrey V. P., Kasper S., Ong D. E., Matusik R. J., Olson G. E., et al. . (2001). Gene duplication gives rise to a new 17-kilodalton lipocalin that shows epididymal region-specific expression and testicular factor(s) regulation. Endocrinology 142, 1296–1308. doi: 10.1210/endo.142.3.8045, PMID: PubMed DOI

Lazar J., Greenwood D. R., Rasmussen L. E. L., Prestwich G. D. (2002). Molecular and functional characterization of an odorant binding protein of the Asian elephant, elephas maximus: implications for the role of lipocalins in mammalian olfaction. Biochemistry 41, 11786–11794. doi: 10.1021/bi0256734, PMID: PubMed DOI

Lechner M., Wojnar P., Redl B. (2001). Human tear lipocalin acts as an oxidative-stress-induced scavenger of potentially harmful lipid peroxidation products in a cell culture system. Biochem. J. 356, 129–135. doi: 10.1042/0264-6021:3560129, PMID: PubMed DOI PMC

Lee Y. C., Liao C., Li P. T., Tzeng W. F., Chu S. T. (2003). Mouse lipocalin as an enhancer of spermatozoa motility. Mol. Biol. Rep. 30, 165–172. doi: 10.1023/A:1024985024661, PMID: PubMed DOI

Lee Y., Mazmanian S. (2010). Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330, 1768–1773. doi: 10.1126/science.1195568, PMID: PubMed DOI PMC

Leinders-Zufall T., Brennan P., Widmayer P., Chandramani P. S., Maul-Pavicic A., Jager M., et al. . (2004). MHC class I peptides as chemosensory signals in the vomeronasal organ. Science 306, 1003–1037. doi: 10.1126/science.1102818, PMID: PubMed DOI

Leinders-Zufall T., Lane A. P., Puche A. C., Ma W., Novotny M. V., Shipley M. T., et al. . (2000). Ultrasensitive pheromone detection by mammalian vomeronasal neurons. Nature 405, 792–796. doi: 10.1038/35015572, PMID: PubMed DOI

Levy D. R., Sofer Y., Brumfeld V., Zilkha N., Kimchi T. (2020). The nasopalatine ducts are required for proper pheromone signaling in mice. Front. Neurosci. 14:585323. doi: 10.3389/fnins.2020.585323, PMID: PubMed DOI PMC

Lilue J., Doran A. G., Fiddes I. T., Abrudan M., Armstrong J., Bennett R., et al. . (2018). Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci. Nat. Genet. 50, 1574–1583. doi: 10.1038/s41588-018-0223-8, PMID: PubMed DOI PMC

Livera G., Rouiller-Fabre V., Pairault C., Levacher C., Habert R. (2002). Regulation and perturbation of testicular functions by vitamin A. Reproduction 124, 173–180. PMID: PubMed

Logan D. W., Marton T. F., Stowers L. (2008). Species specificity in major urinary proteins by parallel evolution. PLoS One 3:e3280. doi: 10.1371/journal.pone.0003280, PMID: PubMed DOI PMC

Loxley G. M., Unsworth J., Turton M. J., Jebb A., Lilley K. S., Simpson D. M., et al. . (2017). Glareosin: a novel sexually dimorphic urinary lipocalin in the bank vole, Myodes glareolus. Open Biol. 7:170135. doi: 10.1098/rsob.170135, PMID: PubMed DOI PMC

Macedo-Marquez A., Vazquez-Acevedo M., Ongay-Larios L., Miranda-Astudillo H., Hernandez-Munoz R., Gonzalez-Halphen D., et al. . (2014). Overexpression of a monomeric form of the bovine odorant-binding protein protects Escherichia coli from chemical-induced oxidative stress. Free Radic. Res. 48, 814–822. doi: 10.3109/10715762.2014.910867, PMID: PubMed DOI

Malnic B., Hirono J., Sato T., Buck L. B. (1999). Combinatorial receptor codes for odors. Cell 96, 713–723. doi: 10.1016/S0092-8674(00)80581-4, PMID: PubMed DOI

Matějková T., Hájková P., Stopková R., Stanko M., Martin J.-F., Kreisinger J., et al. . (2020). Oral and vaginal microbiota in selected field mice of the genus Apodemus: a wild population study. Sci. Rep. 10:13246. doi: 10.1038/s41598-020-70249-x, PMID: PubMed DOI PMC

Miller C. H., Campbell P., Sheehan M. J. (2020). Distinct evolutionary trajectories of V1R clades across mouse species. BMC Evol. Biol. 20:99. doi: 10.1186/s12862-020-01662-z, PMID: PubMed DOI PMC

Mori K., Suzuki T., Minamishima S., Igarashi T., Inoue K., Nishimura D., et al. . (2016). Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice. J. Gastroenterol. Hepatol. 31, 145–154. doi: 10.1111/jgh.13042, PMID: PubMed DOI

Moschen A., Gerner R., Wang J., Klepsch V., Adolph T., Reider S., et al. . (2016). Lipocalin 2 protects from inflammation and tumorigenesis associated with gut microbiota alterations. Cell Host Microbe 19, 455–469. doi: 10.1016/j.chom.2016.03.007, PMID: PubMed DOI

Moss R. L., Flynn R. E., Shen X., Dudley C., Shi J., Novotny M. (1997). Urine-derived compound evokes membrane responses in mouse vomeronasal receptor neurons. J. Neurophysiol. 77, 2856–2862. doi: 10.1152/jn.1997.77.5.2856, PMID: PubMed DOI

Moudra A., Niederlova V., Novotny J., Schmiedova L., Kubovciak J., Matejkova T., et al. . (2021). Phenotypic and clonal stability of antigen-inexperienced memory-like t cells across the genetic background, hygienic status, and aging. J. Immunol. 206, 2109–2121. doi: 10.4049/jimmunol.2001028, PMID: PubMed DOI PMC

Nagel M., Bansal R., Stopka P., Kimchi T., Ben-Shaul Y., Spehr M. (2018). A systematic comparison of semiochemical signaling in the accessory olfactory system of wild and lab strain mice. Chem. Senses 43:E31.

Nagnan-Le Meillour P., Descamps A., Le Danvic C., Grandmougin M., Saliou J.-M., Klopp C., et al. . (2019). Identification of potential chemosignals in the European water vole Arvicola terrestris. Sci. Rep. 9:18378. doi: 10.1038/s41598-019-54935-z, PMID: PubMed DOI PMC

Nagnan-Le Meillour P., Vercoutter-Edouart A. S., Hilliou F., Le Danvic C., Levy F. (2014). Proteomic analysis of pig (Sus scrofa) olfactory soluble proteome reveals O-linked-N-acetylglucosaminylation of secreted odorant-binding proteins. Front. Endocrinol. 5:202. doi: 10.3389/fendo.2014.00202, PMID: PubMed DOI PMC

Nairz M., Schroll A., Sonnweber T., Weiss G. (2010). The struggle for iron – a metal at the host-pathogen interface. Cell. Microbiol. 12, 1691–1702. doi: 10.1111/j.1462-5822.2010.01529.x, PMID: PubMed DOI

Novotny M. V., Jemiolo B., Wiesler D., Ma W., Harvey S., Xu F., et al. . (1999). A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice. Chem. Biol. 6, 377–383. doi: 10.1016/S1074-5521(99)80049-0, PMID: PubMed DOI

Oko R., Morales C. R. (1994). A novel testicular protein, with sequence similarities to a family of lipid binding proteins, is a major component of the rat sperm perinuclear theca. Dev. Biol. 166, 235–245. doi: 10.1006/dbio.1994.1310, PMID: PubMed DOI

Papes F., Logan D. W., Stowers L. (2010). The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141, 692–703. doi: 10.1016/j.cell.2010.03.037, PMID: PubMed DOI PMC

Pelosi P., Zhou J. J., Ban L. P., Calvello M. (2006). Soluble proteins in insect chemical communication. Cell. Mol. Life Sci. 63, 1658–1676. doi: 10.1007/s00018-005-5607-0, PMID: PubMed DOI PMC

Pérez-Gómez A., Bleymehl K., Stein B., Pyrski M., Birnbaumer L., Munger S. D., et al. . (2015). Innate predator odor aversion driven by parallel olfactory subsystems that converge in the ventromedial hypothalamus. Curr. Biol. 25, 1340–1346. doi: 10.1016/j.cub.2015.03.026, PMID: PubMed DOI PMC

Phelan M. M., Mclean L., Armstrong S. D., Hurst J. L., Beynon R. J., Lian L. Y. (2014a). The structure, stability and pheromone binding of the male mouse protein sex pheromone darcin. PLoS One 9:e108415. doi: 10.1371/journal.pone.0108415, PMID: PubMed DOI PMC

Phelan M. M., Mclean L., Hurst J. L., Beynon R. J., Lian L. Y. (2014b). Comparative study of the molecular variation between ‘central’ and ‘peripheral’ MUPs and significance for behavioural signalling. Biochem. Soc. Trans. 42, 866–872. doi: 10.1042/BST20140082, PMID: PubMed DOI

Rankin T. L., Ong D. E., Orgebin-Crist M. C. (1992). The 18-kDa mouse epididymal protein (MEP 10) binds retinoic acid. Biol. Reprod. 46, 767–771. doi: 10.1095/biolreprod46.5.767, PMID: PubMed DOI

Richieri G. V., Ogata R. T., Zimmerman A. W., Veerkamp J. H., Kleinfeld A. M. (2000). Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions. Biochemistry 39, 7197–7204. doi: 10.1021/bi000314z, PMID: PubMed DOI

Riviere S., Challet L., Fluegge D., Spehr M., Rodriguez I. (2009). Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors. Nature 459, 574–577. doi: 10.1038/nature08029, PMID: PubMed DOI

Roberts S. A., Davidson A. J., Mclean L., Beynon R. J., Hurst J. L. (2012). Pheromonal induction of spatial learning in mice. Science 338, 1462–1465. doi: 10.1126/science.1225638, PMID: PubMed DOI

Roberts S. A., Prescott M. C., Davidson A. J., Mclean L., Beynon R. J., Hurst J. L. (2018). Individual odour signatures that mice learn are shaped by involatile major urinary proteins (MUPs). BMC Biol. 16:48. doi: 10.1186/s12915-018-0512-9, PMID: PubMed DOI PMC

Roberts S. A., Simpson D. M., Armstrong S. D., Davidson A. J., Robertson D. H., Mclean L., et al. . (2010). Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male’s odour. BMC Biol. 8:75. doi: 10.1186/1741-7007-8-75, PMID: PubMed DOI PMC

Rodriguez-Martinez H., Saravia F., Wallgren M., Martinez E. A., Sanz L., Roca J., et al. . (2010). Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow. J. Reprod. Immunol. 84, 57–65. doi: 10.1016/j.jri.2009.10.007, PMID: PubMed DOI

Rossitto M., Ujjan S., Poulat F., Boizet-Bonhoure B. (2015). Multiple roles of the prostaglandin D2 signaling pathway in reproduction. Reproduction 149, R49–R58. doi: 10.1530/REP-14-0381, PMID: PubMed DOI

Rutherford S., Bassler B. (2012). Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb. Perspect. Med. 2:a012427. doi: 10.1101/cshperspect.a012427, PMID: PubMed DOI PMC

Sanchez D., Ganfornina M. D., Gutierrez G., Gauthier-Jauneau A. C., Risler J. L., Salier J. P. (2006). “Lipocalin genes and their evolutionary history,” in Lipocalins. eds. Akerstrom B., Borregaard N., Flower A. C. T., Salier J. P. (Georgetown, TX: Landes Bioscience; ), 5–16.

Sanchez D., Ganfornina M. D., Gutierrez G., Marin A. (2003). Exon-intron structure and evolution of the lipocalin gene family. Mol. Biol. Evol. 20, 775–783. doi: 10.1093/molbev/msg079, PMID: PubMed DOI

Santoro S. W., Jakob S. (2018). Gene expression profiling of the olfactory tissues of sex-separated and sex-combined female and male mice. Sci. Data 5:180260. doi: 10.1038/sdata.2018.260, PMID: PubMed DOI PMC

Selvaraj V., Asano A., Page J. L., Nelson J. L., Kothapalli K. S., Foster J. A., et al. . (2010). Mice lacking FABP9/PERF15 develop sperm head abnormalities but are fertile. Dev. Biol. 348, 177–189. doi: 10.1016/j.ydbio.2010.09.019, PMID: PubMed DOI PMC

Seo S., Ahn J., Hong C., Seo E., Kye K., Lee W., et al. . (2006). Expression of neutrophil gelatinase-associated lipocalin in skin epidermis. J. Investig. Dermatol. 126, 510–512. doi: 10.1038/sj.jid.5700035, PMID: PubMed DOI

Sharrow S. D., Novotny M. V., Stone M. J. (2003). Thermodynamic analysis of binding between mouse major urinary protein-I and the pheromone 2-sec-butyl-4,5-dihydrothiazole. Biochemistry 42, 6302–6309. doi: 10.1021/bi026423q, PMID: PubMed DOI

Sharrow S. D., Vaughn J. L., Žídek L., Novotny M. V., Stone M. J. (2002). Pheromone binding by polymorphic mouse major urinary proteins. Protein Sci. 11, 2247–2256. doi: 10.1110/ps.0204202, PMID: PubMed DOI PMC

Sheehan M. J., Campbell P., Miller C. H. (2019). Evolutionary patterns of major urinary protein scent signals in house mice and relatives. Mol. Ecol. 28, 3587–3601. doi: 10.1111/mec.15155, PMID: PubMed DOI

Shi N., Li N., Duan X., Niu H. (2017). Interaction between the gut microbiome and mucosal immune system. Mil. Med. Res. 4:14. doi: 10.1186/s40779-017-0122-9, PMID: PubMed DOI PMC

Shi P., Zhang J. (2007). Comparative genomic analysis identifies an evolutionary shift of vomeronasal receptor gene repertoires in the vertebrate transition from water to land. Genome Res. 17, 166–174. doi: 10.1101/gr.6040007, PMID: PubMed DOI PMC

Singer A., Macrides F., Clancy A. N., Agosta W. C. (1986). Purification and analysis of a proteinaceous aphrodisiac pheromone from hamster vaginal discharge. J. Biol. Chem. 261, 13323–13326. doi: 10.1016/S0021-9258(18)69307-X PubMed DOI

Singh V., Galla S., Golonka R., Patterson A., Chassaing B., Joe B., et al. . (2020). Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice. Physiol. Genomics 52, 314–321. doi: 10.1152/physiolgenomics.00118.2019, PMID: PubMed DOI PMC

Singh V., Yeoh B., Chassaing B., Zhang B., Saha P., Xiao X., et al. . (2016). Microbiota-inducible innate immune, siderophore binding protein lipocalin 2 is critical for intestinal homeostasis. Cell. Mol. Gastroenterol. Hepatol. 4, 482–498.e6. doi: 10.1016/j.jcmgh.2016.03.007 PubMed DOI PMC

Skerget S., Rosenow M. A., Petritis K., Karr T. L. (2015). Sperm proteome maturation in the mouse epididymis. PLoS One 10:e0140650. doi: 10.1371/journal.pone.0140650, PMID: PubMed DOI PMC

Spehr M., Spehr J., Ukhanov K., Kelliher K. R., Leinders-Zufall T., Zufall F. (2006). Parallel processing of social signals by the mammalian main and accessory olfactory systems. Cell. Mol. Life Sci. 63, 1476–1484. doi: 10.1007/s00018-006-6109-4, PMID: PubMed DOI PMC

Stopka P., Janotova K., Heyrovsky D. (2007). The advertisement role of major urinary proteins in mice. Physiol. Behav. 91, 667–670. doi: 10.1016/j.physbeh.2007.03.030, PMID: PubMed DOI

Stopka P., Kuntova B., Klempt P., Havrdova L., Cerna M., Stopkova R. (2016). On the saliva proteome of the eastern European house mouse (Mus musculus musculus) focusing on sexual signalling and immunity. Sci. Rep. 6:32481. doi: 10.1038/srep32481, PMID: PubMed DOI PMC

Stopka P., Macdonald D. W. (1998). Signal interchange during mating in the wood mouse (Apodemus sylvaticus): the concept of active and passive signalling. Behaviour 135, 231–249.

Stopková R., Dudkova B., Hajkova P., Stopka P. (2014). Complementary roles of mouse lipocalins in chemical communication and immunity. Biochem. Soc. Trans. 42, 893–898. doi: 10.1042/BST20140053, PMID: PubMed DOI

Stopková R., Hladovcová D. J. K., Vyoral D., Stopka P. (2009). Multiple roles of secretory lipocalins (MUP, OBP) in mice. Folia Zool. 58, 29–40.

Stopkova R., Klempt P., Kuntova B., Stopka P. (2017). On the tear proteome of the house mouse (Mus musculus musculus) in relation to chemical signalling. PeerJ 5:e3541. doi: 10.7717/peerj.3541, PMID: PubMed DOI PMC

Stopková R., Stopka P., Janotová K., Jedelsky P. L. (2007). Species-specific expression of major urinary proteins in the house mice (Mus musculus musculus and Mus musculus domesticus). J. Chem. Ecol. 33, 861–869. doi: 10.1007/s10886-007-9262-9, PMID: PubMed DOI

Stopková R., Vinkler D., Kuntová B., Sedo O., Albrecht T., Suchan J., et al. . (2016). Mouse lipocalins (MUP, OBP, LCN) are co-expressed in tissues involved in chemical communication. Front. Ecol. Evol. 4:47. doi: 10.3389/fevo.2016.00047 DOI

Stopkova R., Zdrahal Z., Ryba S., Sedo O., Sandera M., Stopka P. (2010). Novel OBP genes similar to hamster Aphrodisin in the bank vole, Myodes glareolus. BMC Genomics 11:45. doi: 10.1186/1471-2164-11-45, PMID: PubMed DOI PMC

Sturm T., Leinders-Zufall T., Macek B., Walzer M., Jung S., Pommerl B., et al. . (2013). Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons. Nat. Commun. 4:1616. doi: 10.1038/ncomms2610, PMID: PubMed DOI

Thoß M., Enk V., Yu H., Miller I., Luzynski K. C., Balint B., et al. . (2016). Diversity of major urinary proteins (MUPs) in wild house mice. Sci. Rep. 6:38378. doi: 10.1038/srep38378, PMID: PubMed DOI PMC

Thoß M., Luzynski K., Ante M., Miller I., Penn D. J. (2015). Major urinary protein (MUP) profiles show dynamic changes rather than individual ‘barcode’ signatures. Front. Ecol. Evol. 3:71. doi: 10.3389/fevo.2015.00071, PMID: PubMed DOI PMC

Thoss M., Luzynski K. C., Enk V. M., Razzazi-Fazeli E., Kwak J., Ortner I., et al. . (2019). Regulation of volatile and non-volatile pheromone attractants depends upon male social status. Sci. Rep. 9:489. doi: 10.1038/s41598-019-41666-4, PMID: PubMed DOI PMC

Tirindelli R. (2021). Coding of pheromones by vomeronasal receptors. Cell Tissue Res. 383, 367–386. doi: 10.1007/s00441-020-03376-6, PMID: PubMed DOI

Turner T. T., Bomgardner D., Jacobs J. P., Nguyen Q. A. (2003). Association of segmentation of the epididymal interstitium with segmented tubule function in rats and mice. Reproduction 125, 871–878. doi: 10.1530/rep.0.1250871, PMID: PubMed DOI

Turton M. J., Robertson D. H. L., Smith J. R., Hurst J. L., Beynon R. J. (2010). Roborovskin, a lipocalin in the urine of the Roborovski hamster, Phodopus roborovskii. Chem. Senses 35, 675–684. doi: 10.1093/chemse/bjq060, PMID: PubMed DOI

Urade Y., Hayaishi O. (2000). Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase. Biochim. Biophys. Acta 1482, 259–271. doi: 10.1016/S0167-4838(00)00161-8, PMID: PubMed DOI

Uroz S., Dessaux Y., Oger P. (2009). Quorum sensing and quorum quenching: the yin and yang of bacterial communication. Chembiochem 10, 205–216. doi: 10.1002/cbic.200800521, PMID: PubMed DOI

Van Der Linden C., Jakob S., Gupta P., Dulac C., Santoro S. W. (2018). Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice. Nat. Commun. 9:5081. doi: 10.1038/s41467-018-07120-1, PMID: PubMed DOI PMC

Vieira F. G., Rozas J. (2011). Comparative genomics of the odorant-binding and chemosensory protein gene families across the arthropoda: origin and evolutionary history of the chemosensory system. Genome Biol. Evol. 3, 476–490. doi: 10.1093/gbe/evr033, PMID: PubMed DOI PMC

Vihani A., Hu X. S., Gundala S., Koyama S., Block E., Matsunami H. (2020). Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic. elife 9:e54501. doi: 10.7554/eLife.54501, PMID: PubMed DOI PMC

Watanabe H., Takeo T., Tojo H., Sakoh K., Berger T., Nakagata N., et al. . (2014). Lipocalin 2 binds to membrane phosphatidylethanolamine to induce lipid raft movement in a PKA-dependent manner and modulates sperm maturation. Development 141, 2157–2164. doi: 10.1242/dev.105148, PMID: PubMed DOI

Wen Z., Liu D., Zhu H., Sun X., Xiao Y., Lin Z., et al. . (2021). Deficiency for Lcn8 causes epididymal sperm maturation defects in mice. Biochem. Biophys. Res. Commun. 548, 7–13. doi: 10.1016/j.bbrc.2021.02.052, PMID: PubMed DOI

Wu H., Santoni-Rugiu E., Ralfkiaer E., Porse B., Moser C., Hoiby N., et al. . (2010). Lipocalin 2 is protective against E. coli pneumonia. Respir. Res. 11:96. doi: 10.1186/1465-9921-11-96, PMID: PubMed DOI PMC

Wynn E. H., Sánchez-Andrade G., Carss K. J., Logan D. W. (2012). Genomic variation in the vomeronasal receptor gene repertoires of inbred mice. BMC Genomics 13:415. doi: 10.1186/1471-2164-13-415, PMID: PubMed DOI PMC

Xiao X., Yeoh B., Vijay-Kumar M., Stover P., Balling R. (2017). Lipocalin 2: an emerging player in iron homeostasis and inflammation. Annu. Rev. Nutr. 37, 103–130. doi: 10.1146/annurev-nutr-071816-064559, PMID: PubMed DOI

Yin Q., Shen J., Wan X., Liu Q., Zhou Y., Zhang Y. (2018). Impaired sperm maturation in conditional Lcn6 knockout mice. Biol. Reprod. 98, 28–41. doi: 10.1093/biolre/iox128, PMID: PubMed DOI

Yip K. S., Suvorov A., Connerney J., Lodato N. J., Waxman D. J. (2013). Changes in mouse uterine transcriptome in estrus and proestrus. Biol. Reprod. 89:13. doi: 10.1095/biolreprod.112.107334, PMID: PubMed DOI PMC

Zala S. M., Bilak A., Perkins M., Potts W. K., Penn D. J. (2015). Female house mice initially shun infected males, but do not avoid mating with them. Behav. Ecol. Sociobiol. 69, 715–722. doi: 10.1007/s00265-015-1884-2 DOI

Zala S. M., Potts W. K., Penn D. J. (2004). Scent-marking displays provide honest signals of health and infection. Behav. Ecol. 15, 338–344. doi: 10.1093/beheco/arh022 DOI

Zhou Z., Feng C., Liu X., Liu S. (2020). 3nLcn2, a teleost lipocalin 2 that possesses antimicrobial activity and inhibits bacterial infection in triploid crucian carp. Fish Shellfish Immunol. 102, 47–55. doi: 10.1016/j.fsi.2020.04.015, PMID: PubMed DOI

Zhou Q., Li Y., Nie R., Friel P., Mitchell D., Evanoff R. M., et al. . (2008). Expression of stimulated by retinoic acid gene 8 (Stra8) and maturation of murine gonocytes and spermatogonia induced by retinoic acid in vitro. Biol. Reprod. 78, 537–545. doi: 10.1095/biolreprod.107.064337, PMID: PubMed DOI PMC

Zidek L., Stone M. J., Lato S. M., Pagel M. D., Miao Z., Ellington A. D., et al. . (1999). NMR mapping of the recombinant mouse major urinary protein I binding site occupied by the pheromone 2-sec-butyl-4,5-dihydrothiazole. Biochemistry 38, 9850–9861. doi: 10.1021/bi990497t, PMID: PubMed DOI

Deciphering the chemical language of inbred and wild mouse conspecific scents

The Expansion of House Mouse Major Urinary Protein Genes Likely Did Not Facilitate Commensalism with Humans

Variation in mouse chemical signals is genetically controlled and environmentally modulated

Sperm morphology and performance in relation to postmating prezygotic isolation in two recently diverged passerine species