Adcyap1r1-KO 基因敲除小鼠

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产品名称

Adcyap1r1-KO 基因敲除小鼠

产品编号

S-KO-00922

品系全称

C57BL/6NCya-Adcyap1r1em1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-11517-Adcyap1r1-B6N-VA

品系状态

使用本品系发表的文献需注明: Adcyap1r1-KO 基因敲除小鼠 mice (Strain S-KO-00922) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
adenylate cyclase activating polypeptide 1 receptor 1
基因别称
2900024I10Rik,PAC1,PAC1R,PACAP1-R
染色体号
Chr 6 (Mouse)
转录本 ID
NCBI: NM_007407 | Ensembl: ENSMUST00000070736
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~0.1 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:108449Homozygotes for targeted mutations affect contextual fear conditioning, elevated locomotor activity, anxiety-like behavior, susceptibility to endotoxic shock, circadian responses to a photic stimulus, and glucose tolerance. Some alleles affect female fertility.

发表文献

Scientific Reports
2026-05-26
Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes regeneration of corneal epithelial cells possibly via the NR4A1 signaling pathway
1
Adcyap1r1,即腺苷酸环化酶活化多肽1受体1(pituitary)基因,编码了一种与下丘脑-垂体-肾上腺(HPA)轴相关的受体。HPA轴是控制应激反应的重要调节系统,Adcyap1r1基因的变异与应激反应有关,尤其是与创伤后应激障碍(PTSD)的发病机制相关[1][2][3][4][5][6][7][8]。Adcyap1r1基因中的单核苷酸多态性(SNP)rs2267735已经被广泛研究,以确定其与PTSD的关联性。

在许多研究中,rs2267735与PTSD的关联性并不一致。一些研究表明,C等位基因的rs2267735与PTSD的风险增加有关,尤其是在女性和女孩中[2][7]。然而,也有研究并未发现显著的关联性[1][3]。这些不一致的结果表明,Adcyap1r1基因对PTSD的影响可能受到其他基因的相互作用、性别、创伤暴露和社会环境等因素的影响。

此外,Adcyap1r1基因的表达受到雌激素的调节。研究发现,rs2267735位于一个预测的雌激素反应元件(ERE)内,该元件可以调节基因转录[7]。在女性中,当雌激素水平较低时,CC基因型与Adcyap1r1表达降低有关,并且与PTSD症状增加相关[7]。这表明,雌激素调节的Adcyap1r1基因表达可能作为应激反应的适应性机制,而rs2267735风险等位基因的抑制可能降低了这种适应性反应,从而增加了PTSD的风险。

除了PTSD,Adcyap1r1基因还与焦虑、哮喘和其他精神疾病有关[8]。例如,在波多黎各儿童中,Adcyap1r1基因的表观遗传变异与哮喘发病相关[8]。这些研究结果进一步支持了Adcyap1r1基因在应激反应和心理健康中的重要作用。

综上所述,Adcyap1r1基因在应激反应和PTSD的发病机制中发挥着重要作用。rs2267735变异与PTSD风险增加有关,尤其是在女性中。此外,Adcyap1r1基因的表达受到雌激素的调节,雌激素水平的降低可能导致PTSD风险增加。这些研究结果为理解PTSD的遗传和环境因素提供了重要的见解,并为开发针对PTSD的治疗策略提供了潜在的目标。

参考文献:
1. Wang, Li, Zhang, Jingyi, Li, Gen, Zhang, Yingqian, Zhang, Kunlin. 2021. The ADCYAP1R1 Gene Is Correlated With Posttraumatic Stress Disorder Symptoms Through Diverse Epistases in a Traumatized Chinese Population. In Frontiers in psychiatry, 12, 665599. doi:10.3389/fpsyt.2021.665599. https://pubmed.ncbi.nlm.nih.gov/34163384/
2. Lind, Mackenzie J, Marraccini, Marisa E, Sheerin, Christina M, Amstadter, Ananda B, Nugent, Nicole R. 2017. Association of Posttraumatic Stress Disorder With rs2267735 in the ADCYAP1R1 Gene: A Meta-Analysis. In Journal of traumatic stress, 30, 389-398. doi:10.1002/jts.22211. https://pubmed.ncbi.nlm.nih.gov/28746747/
3. Zhang, Jingyi, Li, Gen, Yang, Haibo, Zhang, Kunlin, Wang, Li. 2022. The main effect and gene-environment interaction effect of the ADCYAP1R1 polymorphism rs2267735 on the course of posttraumatic stress disorder symptoms-A longitudinal analysis. In Frontiers in psychiatry, 13, 1032837. doi:10.3389/fpsyt.2022.1032837. https://pubmed.ncbi.nlm.nih.gov/36386994/
4. Lowe, Sarah R, Pothen, John, Quinn, James W, Ressler, Kerry J, Koenen, Karestan C. 2015. Gene-by-social-environment interaction (GxSE) between ADCYAP1R1 genotype and neighborhood crime predicts major depression symptoms in trauma-exposed women. In Journal of affective disorders, 187, 147-50. doi:10.1016/j.jad.2015.08.002. https://pubmed.ncbi.nlm.nih.gov/26334183/
5. Jovanovic, Tanja, Stenson, Anaïs F, Thompson, Nadia, Bradley, Bekh, Ressler, Kerry J. 2020. Impact of ADCYAP1R1 genotype on longitudinal fear conditioning in children: interaction with trauma and sex. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 45, 1603-1608. doi:10.1038/s41386-020-0748-2. https://pubmed.ncbi.nlm.nih.gov/32590837/
6. Bevilacqua, Laura, Goldman, David. 2011. Genetics of emotion. In Trends in cognitive sciences, 15, 401-8. doi:10.1016/j.tics.2011.07.009. https://pubmed.ncbi.nlm.nih.gov/21835681/
7. Mercer, K B, Dias, B, Shafer, D, Walton, J, Ressler, K J. 2016. Functional evaluation of a PTSD-associated genetic variant: estradiol regulation and ADCYAP1R1. In Translational psychiatry, 6, e978. doi:10.1038/tp.2016.241. https://pubmed.ncbi.nlm.nih.gov/27959335/
8. Chen, Wei, Boutaoui, Nadia, Brehm, John M, Canino, Glorisa, Celedón, Juan C. 2013. ADCYAP1R1 and asthma in Puerto Rican children. In American journal of respiratory and critical care medicine, 187, 584-8. doi:10.1164/rccm.201210-1789OC. https://pubmed.ncbi.nlm.nih.gov/23328528/

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