| 1331373 | Assignments of the genes for rat pituitary adenylate cyclase activating polypeptide (Adcyap1) and its receptor subtypes (Adcyap1r1, Adcyap1r2, and Adcyap1r3). | Cai Y, etal., Cytogenet Cell Genet 1995;71(2):193-6. | Chromosomal assignments of the genes for rat pituitary adenylate cyclase activating polypeptide (Adcyap1) and all of its receptor subtypes (Adcyap1r1, Adcyap1r2, and Adcyap1r3) were performed by PCR analysis of somatic cell hybrid DNAs. Adcyap1r1 700;'>Adcyap1r1, Adcyap1r2, and Adcyap1r3 were localized to rat chromosomes 9, 4, 8, and 4, respectively. | 7656595 | 1995-01-01 |
| 407984966 | Estrogen-Dependent Upregulation of Adcyap1r1 Expression in Nucleus Accumbens Is Associated With Genetic Predisposition of Sex-Specific QTL for Alcohol Consumption on Rat Chromosome 4. | Spence JP, etal., Front Genet. 2018 Dec 4;9:513. doi: 10.3389/fgene.2018.00513. eCollection 2018. | Humans show sex differences related to alcohol use disorders (AUD). Animal model research has the potential to provide important insight into how sex differences affect alcohol consumption, particularly because female animals frequently drink more than males. In previous work, inbred strains of the selectively bred alcohol-preferring (P) and non-preferring (NP) rat lines revealed a highly significant quantitative trait locus (QTL) on rat chromosome 4, with a logarithm of the odds score of 9.2 for alcohol consumption. Recently, interval-specific congenic strains (ISCS) were developed by backcrossing the congenic P.NP line to inbred P (iP) rats to further refine the chromosome 4 QTL region. Two ISCS sub-strains, ISCS-A and ISCS-B, were obtained with a narrowed QTL, where the smallest region of overlap consisted of 8.9 Mb in ISCS-B. Interestingly, we found that females from both ISCS lines consumed significantly less alcohol than female iP controls (p < 0.05), while no differences in alcohol consumption were observed between male ISCS and iP controls. RNA-sequencing was performed on the nucleus accumbens of alcohol-naïve female ISCS-B and iP rats, which revealed differentially expressed genes (DEG) with greater than 2-fold change and that were functionally relevant to behavior. These DEGs included down-regulation of Oxt, Asb4, Gabre, Gabrq, Chat, Slc5a7, Slc18a8, Slc10a4, and Ngfr, and up-regulation of Ttr, Msln, Mpzl2, Wnt6, Slc17a7, Aldh1a2, and Gstm2. Pathway analysis identified significant alterations in gene networks controlling nervous system development and function, as well as cell signaling, GABA and serotonin receptor signaling and G-protein coupled receptor signaling. In addition, β-estradiol was identified as the most significant upstream regulator. The expression levels of estrogen-responsive genes that mapped to the QTL interval and have been previously associated with alcohol consumption were measured using RT-qPCR. We found that expression of the Adcyap1r1 gene, encoding the pituitary adenylate cyclase-activating polypeptide type 1 (PAC1) receptor, was upregulated in female ISCS-B compared to female iP controls, while no differences were exhibited in males. In addition, sequence variants in the Adcyap1r1 promoter region showed a differential response to estrogen stimulation in vitro. These findings demonstrate that rat chromosome 4 QTL contains genetic variants that respond to estrogen and are associated with female alcohol consumption. | 30564267 | 2018-12-01 |
| 11097396 | Gene-by-social-environment interaction (GxSE) between ADCYAP1R1 genotype and neighborhood crime predicts major depression symptoms in trauma-exposed women. | Lowe SR, etal., J Affect Disord. 2015 Nov 15;187:147-50. doi: 10.1016/j.jad.2015.08.002. Epub 2015 Aug 28. | BACKGROUND: Few studies have explored interactions between genes and social environmental exposures (GxSEs) for trauma-related psychopathology, including symptoms of posttraumatic stress (PTS) and major depression (MD). The extant literature suggests the possibility of a GxSE between the rs2267735 v ariant of the ADCYAP1R1 gene and neighborhood crime. The current study aimed to explore this possibility among a predominantly African American sample of trauma-exposed women. METHODS: Female participants (N=1361) were recruited from a public hospital, and completed measures of PTS and MD symptoms and provided DNA samples. Participants' home addresses were mapped onto 300 neighborhoods (2010 census tracts), and data on crime within neighborhoods was collected. RESULTS: Multilevel models detected a significant GxSE between rs2267735 and neighborhood crime for MD symptoms (p=.01). Having two copies of the risk (C) allele was associated with higher MD symptoms for participants living in high-crime neighborhoods. LIMITATIONS: At least six limitations are noteworthy: (1) low statistical power; (2) use of self-report symptom inventories; (3) lack of information on symptom onset; (4) homogeneous sample from a single metropolitan area; (5) non-specific index of crime; and (6) use of census tracts to define neighborhoods. CONCLUSIONS: The results provide further evidence of GxSEs for psychiatric outcomes among trauma-exposed populations. Further investigations of genetic factors for trauma-related psychopathology should include careful assessments of the social environment. | 26334183 | 2015-06-01 |
