Faah-KO 基因敲除小鼠

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产品名称

Faah-KO 基因敲除小鼠

产品编号

S-KO-01983

品系全称

C57BL/6JCya-Faahem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-14073-Faah-B6J-VA

品系状态

使用本品系发表的文献需注明: Faah-KO 基因敲除小鼠 mice (Strain S-KO-01983) 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
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
全身性基因敲除
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.
Fatty acid amide hydrolase (FAAH) 是一种关键的酶,负责降解内源性大麻素系统中的主要信号分子——花生四烯酸乙醇胺(anandamide,AEA)。FAAH在调节情绪、疼痛、食欲和新陈代谢等方面发挥着重要作用。近年来,对FAAH基因的研究不断深入,揭示了其与多种疾病和生理功能之间的关联。

FAAH基因的编码产物——FAAH酶,具有广泛的底物特异性,能够水解多种N-酰基乙醇胺,包括AEA和2-AG。AEA是一种内源性的大麻素受体激动剂,能够激活大麻素受体1(CB1R),进而调节多巴胺的释放,影响情绪和幸福感。研究发现,FAAH基因的遗传变异与主观幸福感直接相关。具体来说,rs324420位点的A等位基因与FAAH活性的降低和AEA水平的升高相关,进而与较低的主观幸福感评分相关[1]。

此外,FAAH基因的遗传变异还与多种神经精神疾病相关。研究发现,rs324420位点的A等位基因与焦虑和抑郁症状的严重程度相关。在创伤后应激障碍(PTSD)患者中,FAAH C385A等位基因的携带者表现出对压力挑战的焦虑反应降低,并伴随着血清AEA水平的升高[7]。此外,FAAH基因的变异还与酒精依赖、注意力缺陷多动障碍(ADHD)和癫痫等疾病相关[3,5,6]。

除了遗传变异,FAAH的表达还受到表观遗传调控的影响。研究发现,早期生活应激和青春期应激能够通过DNA甲基化等机制影响FAAH和CB1R的表达,进而影响个体的应激反应和情绪行为[4]。此外,长非编码RNA(lncRNA)FAAH-OUT也被发现能够调控FAAH的表达,进而影响个体的疼痛敏感性和焦虑水平[2]。

综上所述,FAAH基因在调节情绪、疼痛、食欲和新陈代谢等方面发挥着重要作用。FAAH基因的遗传变异和表观遗传调控与多种疾病和生理功能相关,为疾病的治疗和预防提供了新的思路和策略。未来研究可以进一步探究FAAH基因的生物学功能和作用机制,以及其在临床应用中的潜在价值。

参考文献:
1. 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/
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. 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/
4. 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/
5. 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/
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. 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/