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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 (-/-) 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 -/- 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 -/- animals, suggesting monomer instability. Overall, we observed no major phenotypic changes in the -/- genotype, compared with their +/+ and +/- 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.

SUBMITTER: Chung AG

PROVIDER: S-EPMC5378110 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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

Chung Amanda G AG Belone Phillip M PM Bímová Barbora Vošlajerová BV Karn Robert C RC Laukaitis Christina M CM

Genetics 20170203 4

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< ...[more]

PMID: 28159752

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Project description:BackgroundSpermatogenesis is an androgen-dependent process, yet the molecular mechanisms of androgens' actions in testis are poorly understood. Transgenic mice overexpressing rat androgen-binding protein (ABP) in their testes have reduced levels of intratesticular androgens and, as a result, show a progressive impairment of spermatogenesis. We used this model to characterize changes in global gene expression in testis in response to reduced bioavailability of androgens.MethodsTotal RNA was extracted from testes of 30-day old transgenic and wild-type control mice, converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays. Microarray results were confirmed by real-time reverse transcription polymerase chain reaction.ResultsThree-hundred-eighty-one genes (3.05% of all transcripts represented on the chips) were up-regulated and 198 genes (1.59%) were down-regulated by at least a factor of 2 in the androgen-deficient animals compared to controls. Genes encoding membrane proteins, intracellular signaling molecules, enzymes, proteins participating in the immune response, and those involved in cytoskeleton organization were significantly overrepresented in the up-regulated group. Among the down-regulated transcripts, those coding for extracellular proteins were overrepresented most dramatically, followed by those related to proteolysis, cell adhesion, immune response, and growth factor, cytokine, and ion channel activities. Transcripts with the greatest potential impact on cellular activities included several transcription factors, intracellular signal transducers, secreted signaling molecules and enzymes, and various cell surface molecules. Major nodes in the up-regulated network were IL-6, AGT, MYC, and A2M, those in the down-regulated network were IL-2, -4, and -10, MAPK8, SOCS1, and CREB1.ConclusionMicroarray analysis followed by gene ontology profiling and connectivity analysis identified several functional groups of genes and individual genes responding to sustained reduction of androgen levels in the mouse testis. These include genes whose products function as transcription factors, cell surface molecules including ion channels, extra- and intracellular signaling molecules, and secreted enzymes with the potential of regulating cell-to-cell attachment. The transcription factors CREB1 (down-regulated) and MYC (up-regulated) may mediate the most important initial phases of the testicular response to reduced levels of androgens. These results suggest specific avenues for further research that will lead to a better understanding of how androgens regulate spermatogenesis.

Dataset Information

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

Publications

Studies of an <i>Androgen-Binding Protein</i> Knockout Corroborate a Role for Salivary ABP in Mouse Communication.

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