Faah-flox 基因敲除小鼠

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产品名称

Faah-flox 基因敲除小鼠

产品编号

S-CKO-02332

品系全称

C57BL/6JCya-Faahem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-14073-Faah-B6J-VA

品系状态

使用本品系发表的文献需注明: Faah-flox 基因敲除小鼠 mice (Strain S-CKO-02332) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
fatty acid amide hydrolase
基因别称
-
染色体号
Chr 4 (Mouse)
转录本 ID
NCBI: NM_010173 | Ensembl: ENSMUST00000049095
修饰方式
条件性基因敲除
靶向范围
Exon 8~9
敲除长度
~1.4 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:109609Homozygotes for a null allele show high brain anandamide (AEA) levels, reduced pain sensation, altered behavioral responses to AEA, and sex-specific changes in ethanol intake and sensitivity. Homozygotes for the C385A variant show enhanced cued fear extinction and reduced anxiety-like behavior.
FAAH,全称为脂肪酸酰胺水解酶(Fatty Acid Amide Hydrolase),是一种存在于人体内的关键酶,负责降解内源性大麻素系统中的主要神经递质——花生四烯酸酰胺(Anandamide,AEA)。FAAH的活性变化会影响AEA的水平,进而影响神经系统的多种功能,包括情绪、疼痛感知、记忆和认知等。研究表明,FAAH的基因变异与多种神经精神疾病的发生和发展有关,如焦虑症、抑郁症、精神分裂症等[1][2][3][4][5][6][7][8][9][10]。

研究发现,FAAH基因的某些多态性(如rs324420)与焦虑症、抑郁症和酒精依赖等疾病的风险相关[3][8]。例如,rs324420位点的A等位基因与AEA水平的升高有关,而AEA水平的升高与焦虑症、抑郁症和酒精依赖等疾病的风险增加相关[3][8]。此外,FAAH基因的表达还受到表观遗传调控的影响,如DNA甲基化和组蛋白修饰等[5][6][7]。

FAAH基因的变异还与疼痛感知有关。研究发现,FAAH-OUT基因(一种位于FAAH基因附近的非编码RNA基因)的突变会导致FAAH基因表达下调,从而降低疼痛感知[2]。此外,FAAH基因的表达还受到早期生活应激和青春期应激的影响,进而影响疼痛感知和情绪行为[5][6]。

除了神经精神疾病和疼痛感知外,FAAH基因的变异还与物质使用障碍有关。研究发现,FAAH基因的某些多态性与实验性物质使用、冲动性和寻求刺激的行为有关[6][7]。此外,FAAH基因的表达还与暴食症的发生有关,研究表明,暴食症患者体内AEA和2-AG(另一种内源性大麻素)的水平升高,而FAAH基因的表达下调[7]。

综上所述,FAAH基因在神经系统的多种功能中发挥着重要作用。FAAH基因的变异与多种神经精神疾病、疼痛感知和物质使用障碍等疾病的发生和发展有关。深入研究FAAH基因的功能和调控机制,有助于我们更好地理解这些疾病的发病机制,并为开发新的治疗策略提供理论基础。

参考文献:
1. Hashimoto, Kenji. . Impact of FAAH gene, hyperactivation in emotion processing brain regions and Lavender oil preparation Silexan in anxiety. In European archives of psychiatry and clinical neuroscience, 269, 145-146. doi:10.1007/s00406-019-00987-1. https://pubmed.ncbi.nlm.nih.gov/30680488/
2. Mikaeili, Hajar, Habib, Abdella M, Yeung, Charlix Wai-Lok, Okorokov, Andrei L, Cox, James J. . Molecular basis of FAAH-OUT-associated human pain insensitivity. In Brain : a journal of neurology, 146, 3851-3865. doi:10.1093/brain/awad098. https://pubmed.ncbi.nlm.nih.gov/37222214/
3. Bornscheuer, Lisa, Lundin, Andreas, Forsell, Yvonne, Lavebratt, Catharina, Melas, Philippe A. 2023. Functional Variation in the FAAH Gene Is Directly Associated with Subjective Well-Being and Indirectly Associated with Problematic Alcohol Use. In Genes, 14, . doi:10.3390/genes14091826. https://pubmed.ncbi.nlm.nih.gov/37761966/
4. Anvar, Leila Hosseinzadeh, Alejafar, Asghar, Moosavi, Seyyed Ebrahim, Nikanfar, Masoud, Ahmadalipour, Ali. 2023. The study of rs324420 (C385A) polymorphism of the FAAH gene of the endocannabinoid system in patients with epilepsy and ADHD. In Epilepsy research, 192, 107100. doi:10.1016/j.eplepsyres.2023.107100. https://pubmed.ncbi.nlm.nih.gov/37018974/
5. Demaili, Arijana, Portugalov, Anna, Dudai, Michal, Braun, Katharina, Bock, Jörg. 2023. Epigenetic (re)programming of gene expression changes of CB1R and FAAH in the medial prefrontal cortex in response to early life and adolescence stress exposure. In Frontiers in cellular neuroscience, 17, 1129946. doi:10.3389/fncel.2023.1129946. https://pubmed.ncbi.nlm.nih.gov/36909279/
6. Huertas, Evelio, López-Moreno, José A, Fernández, Vanessa, Echeverry-Alzate, Víctor, Bühler, Kora-M. . Associations between experimental substance use, FAAH-gene variations, impulsivity and sensation seeking. In Psicothema, 31, 239-245. doi:10.7334/psicothema2019.27. https://pubmed.ncbi.nlm.nih.gov/31292037/
7. Yagin, Neda Lotfi, Aliasgari, Fereshteh, Alizadeh, Mohammad, Aliasgharzadeh, Soghra, Mahdavi, Reza. 2020. Comparison of endocannabinoids levels, FAAH gene polymorphisms, and appetite regulatory substances in women with and without binge eating disorder: a cross- sectional study. In Nutrition research (New York, N.Y.), 83, 86-93. doi:10.1016/j.nutres.2020.09.001. https://pubmed.ncbi.nlm.nih.gov/33038759/
8. Spagnolo, Primavera A, Ramchandani, Vijay A, Schwandt, Melanie L, Hillard, Cecilia J, Heilig, Markus. 2016. FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence. In Alcoholism, clinical and experimental research, 40, 2426-2434. doi:10.1111/acer.13210. https://pubmed.ncbi.nlm.nih.gov/27716956/
9. Guerin, Alexandre A, Spolding, Briana, Bozaoglu, Kiymet, Walder, Ken, Kim, Jee Hyun. 2024. Associations between methamphetamine use disorder and SLC18A1, SLC18A2, BDNF, and FAAH gene sequence variants and expression levels. In Dialogues in clinical neuroscience, 26, 64-76. doi:10.1080/19585969.2024.2413476. https://pubmed.ncbi.nlm.nih.gov/39394974/
10. Hryhorowicz, Szymon, Walczak, Michal, Zakerska-Banaszak, Oliwia, Słomski, Ryszard, Skrzypczak-Zielińska, Marzena. . Pharmacogenetics of Cannabinoids. In European journal of drug metabolism and pharmacokinetics, 43, 1-12. doi:10.1007/s13318-017-0416-z. https://pubmed.ncbi.nlm.nih.gov/28534260/