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

Abstract

The house mouse Androgen-binding protein (Abp) gene family is comprised of 64 paralogs, 30 Abpa and 34 Abpbg, encoding the alpha (ABPA) and beta-gamma (ABPBG) protein subunits that are disulfide-bridged to form dimers in secretions. Only 14 Abp genes are expressed in distinct patterns in the lacrimal (11) and submandibular glands (3). We created a knockout mouse line lacking two of the three genes expressed in submandibular glands, Abpa27 and Abpbg27, by replacing them with the neomycin resistance gene. The knockout genotype (2/2) showed no Abpa27 or Abpbg27 transcripts in submandibular gland complementary DNA (cDNA) libraries and there was a concomitant lack of protein expression of ABPA27 and ABPBG27 in the 2/2 genotype saliva, shown by elimination of these two proteins from the saliva proteome and the loss of cross-reactive material in the acinar cells of the submandibular glands. We also observed a decrease in BG26 protein in the 2/2 animals, suggesting monomer instability. Overall, we observed no major phenotypic changes in the 2/2 genotype, compared with their +/+ and +/2 siblings raised in a laboratory setting, including normal growth curves, tissue histology, fecundity, and longevity. The only difference is that male and female C57BL/6 mice preferred saliva of the opposite sex containing ABP statistically significantly more than saliva of the opposite sex without ABP in a Y-maze test. These results show for the first time that mice can sense the presence of ABP between saliva targets with and without ABPs, and that they spend more time investigating the target containing ABP.

Transcriptional profiling reveals gland-specific differential expression in the three major salivary glands of the adult mouse

“…We also noticed HEGsassociated GO terms that were unevenly distributed across the three glands. For instance, molecular function GO:0005497 (androgen binding) was only associated with the HEGs in SMG, a gland known to be androgen sensitive (7). The biological process GO:0006888 (ER to Golgi vesicle-mediated transport) was only associated with the HEGs in SLG, where these ER-Golgi intermediate compartment proteins are highly expressed, as well as in other mucous cells (45).…”

Another cat and mouse game: Deciphering the evolution of the SCGB superfamily and exploring the molecular similarity of major cat allergen Fel d 1 and mouse ABP using computational approaches

“…Additionally, the AB and AG dimers exhibited equivalent interactions with P. The differential affinities of the ABP dimers suggest that stimulus preferences are involved in adaptive evolution and influence mate choice [ 73 ]. Recently, Chung et al (2017) demonstrated in a knockout study that mice are capable of detecting the presence/absence of ABP in saliva from the opposite sex, supporting a role of ABP in intraspecific chemical communication [ 44 ]. In addition, previous studies demonstrated a close association of Fel d 1 production areas and pheromone releasing areas in cats and showed that cat sex and behavior affect the immunological properties of Fel d 1, which suggested that Fel d 1 could be involved in feline chemical communication [ 18 ], [ 34 ].…”

“…Mouse salivary ABP is considered to be a proteinaceous pheromone that mediates assortative mate selection. The three ABP subunits (ABPA27, ABPBG27, and ABPBG26) form A27:BG27 (AB) and A27:BG26 (AG) dimers in the saliva’s of both sexes, and experiments using an Abpa27-Abpbg27 knockout strain have shown that these genes are required for ABP-based recognition [ 44 ]. Assortative mate choice based on this subspecies recognition mechanism leads to reinforcement in the European mouse hybrid zone where the two subspecies meet [ 45 ], [ 46 ].…”

The Major Cat Allergen Fel d 1 Binds Steroid and Fatty Acid Semiochemicals: A Combined In Silico and In Vitro Study

“…From a structural perspective, Fel d 1 also displays interesting features regarding ligand binding capabilities due to the presence of two internal cavities [23]. Structural similarities between Fel d 1 and another secretoglobin involved in mice mate selection and communication, the mouse salivary androgen-binding protein (ABP) [18], have been previously described [24,25]. Binding of some steroids to members of the secretoglobin family was previously reported, involving interactions with their central hydrophobic cavity [19,23,26].…”

“…For other members of the secretoglobin family, different biological roles have been suggested, mainly related to immunoregulation [13][14][15][16], but also in chemical signaling [17][18][19]. Also for Fel d 1, a role in intra-species chemical communication has been proposed based on the fact that the protein is produced in the same areas known to release the cat semiochemicals, including the facial area, the podial complex, and the perianal zone, which contain glands that secrete chemical cues involved in cat territorial marking and/or social communication [20,21].…”