Academic journal article Genetics

Studies of an Androgen-Binding Protein Knockout Corroborate a Role for Salivary ABP in Mouse Communication

Academic journal article Genetics

Studies of an Androgen-Binding Protein Knockout Corroborate a Role for Salivary ABP in Mouse Communication

Article excerpt

PERHAPS the most important theme in biology involves the relationship of structure and function. The difficulties one can encounter in resolving this relationship for a particular structure(s) are illustrated by the proteins that comprise the secretoglobin superfamily. Secretoglobins are defined by a four-helix bundle in a boomerang configuration called the secretoglobin fold [for a review see Mukerjhee and Chilton (2000)]. Even 50 years after the discovery of the first member of this family, uteroglobin [UG, reviewed in Beier (2000)], most superfamily members still do not have unequivocal functions attributed to them. The Androgen-binding proteins (ABPs; Dlouhy and Karn 1984) are a mammalian novelty originally discovered in mouse saliva (Emes et al. 2004; Laukaitis et al. 2008). They are dimers composed of an alpha subunit disulfide-bridged to a beta-gamma subunit, both of which have the secretoglobin fold (Karn and Laukaitis 2003; Laukaitis and Karn 2005). The two mouse salivary ABP dimers share an alpha-subunit encoded by Abpa27 (a27) bound to a second subunit encoded by either Abpbg27 (bg27) or Abpbg26 (bg26). The function(s) ofthese proteins has been the topic of research for the past 20 years [reviewed in Laukaitis and Karn (2012)].

A great deal of interest has been focused on three rodent pheromone protein families encoded by genes that have undergone extensive gene duplication in mice (Karn and Laukaitis 2009). Some of the proteins encoded by these gene families affect mate selection, thus directly impacting gene exchange and thereby evolution and potentially speciation. These three gene families encode the ABPs, the exocrine gland-secreting peptides (ESPs), and the major urinary proteins (MUPs). ABP-mediated assortative mate selection based on subspecies recognition potentially limits gene exchange between subspecies where they meet (Laukaitis et al. 1997; Talley et al. 2001) and there is evidence that ABP constitutes a system of incipient reinforcement where subspecies make secondary contact, the house mouse hybrid zone in Europe (Bímová et al 2005; Voslajerová Bímová et al. 2011). ESPs are small rodent proteinaceous pheromones (Kimoto et al. 2005). Female mice respond to direct facial exposure to an ESP found in male tear fluid by upregulating c-Fos and Egr1 gene expression in vomeronasal sensory neurons (Kimoto and Touhara 2005; Kimoto et al. 2007), and there is evidence that mouse ESP1 enhances female sexual receptive behavior, lordosis, upon male mounting and copulation (Haga et al. 2010). The MUPs are a family of lipocalins shown to mediate female recognition of potential mates [for a review, see Hurst (2009)]. Each adult mouse expresses a pattern of 8-14 different MUP isoforms in its urine, which is determined by its genotype and by its sex, that has been likened to a protein "bar code" (Robertson et al. 1996; Beynon and Hurst 2003; Armstrong et al. 2005; Cheetham et al. 2007; Logan et al. 2008). In addition to causing a female to develop sexual attraction to a male (Roberts et al. 2010), MUPs have been implicated in male-male aggression (Stowers et al. 2002; Chamero et al 2007) and accelerating puberty in female mice (Clissold et al. 1984; Clark et al. 1985; Mucignat Caretta et al. 1995).

Early studies of the function of ABP drew on population genetic work that suggested that different a27 alleles are fixed in each of the three subspecies of Mus musculus [a27a in M. m. domesticus (western Europe and the Mediterranean basin), a27b in M. m. musculus (eastern Europe to northern China), and a27c in M. m.castaneus (Southeast Asia and Malaysia); (Karn and Dlouhy 1991; Karn et al. 2002)]. This unusual a27 monomorphism in each of the three subspecies and the existence of a relatively narrow house mouse hybrid zone between M. m. domesticus and M. m. musculus in Europe [reviewed in Baird and Macholán (2012)] suggested that ABP might have a role in mediating subspecies recognition. That led to the production of congenic strains, one with a27a from M. …

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