Cyp11a1-KO 基因敲除小鼠

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产品名称

Cyp11a1-KO 基因敲除小鼠

产品编号

S-KO-20430

品系全称

C57BL/6JCya-Cyp11a1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-13070-Cyp11a1-B6J-VA

品系状态

使用本品系发表的文献需注明: Cyp11a1-KO 基因敲除小鼠 mice (Strain S-KO-20430) 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
cytochrome P450, family 11, subfamily a, polypeptide 1
基因别称
Cyp11a,Cypxia1,D9Ertd411e,P450scc,Scc,cscc
染色体号
Chr 9 (Mouse)
转录本 ID
NCBI: NM_019779 | Ensembl: ENSMUST00000034874
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~0.9 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:88582Homozygous null mice are exhibit a steroid deficiency and die within days of birth showing signs of dehydration. Males are feminized with female external genitalia and underdeveloped gonads. Mice homozgyous for another knock-out allele exhibit abnormal adrenal development and neonatal lethality.
CYP11A1,也称为细胞色素P450scc,是一种位于线粒体内膜的酶,负责催化胆固醇转化为孕烯醇酮的第一步反应,这是类固醇生物合成的限速步骤[1]。CYP11A1的表达受多种转录因子的调控,包括SF-1、Sp1、AP-2、TReP-132、LBP-1b、LBP-9、AP-1、NF-1和Ets,这些因子通过与CYP11A1基因启动子区域的特定顺式作用元件结合,或者通过蛋白质-蛋白质相互作用,来调节CYP11A1的转录[9]。其中,SF-1在肾上腺和睾丸中发挥着核心作用,通过与TFIIB、CBP/p300、TReP-132和c-Jun/AP-1等蛋白质相互作用,来特异性地传递cAMP信号,从而调控CYP11A1的转录[9]。

CYP11A1的表达在肾上腺和性腺中受到激素的严格控制,其表达水平的变化与类固醇激素的合成密切相关。例如,在猪的子宫中,促生长素A(OXA)能够通过调节CYP11A1等关键类固醇生成酶的基因表达,以及调节孕酮和雄烯二酮的分泌,来影响妊娠早期和发情周期的类固醇激素合成[4]。此外,CYP11A1的表达还与多种疾病的发生发展相关。例如,在多囊卵巢综合征(PCOS)患者中,CYP11A1基因的突变或表达异常会导致类固醇激素合成失调,进而引发PCOS的相关症状[3,8]。此外,CYP11A1的表达还与自闭症谱系障碍(ASD)的发生相关,研究表明,CYP11A1基因的突变或表达异常可能会导致ASD的发生[6]。

CYP11A1除了参与类固醇激素的合成外,还参与调节线粒体的结构和功能。研究表明,CYP11A1的表达能够改变线粒体的结构,使其形成管状和囊泡状的嵴[7]。CYP11A1的A'-螺旋结构域是线粒体结构重塑的关键区域,其插入膜中并改变嵴的形成[7]。CYP11A1还与热休克蛋白60(Hsp60)相互作用,Hsp60是CYP11A1积累和线粒体嵴重塑所必需的[7]。

综上所述,CYP11A1是一种重要的类固醇生成酶,参与调节类固醇激素的合成和线粒体的结构和功能。CYP11A1的表达受到多种转录因子的调控,其表达水平的变化与多种疾病的发生发展相关。CYP11A1的研究有助于深入理解类固醇激素的合成机制、线粒体功能的调控机制以及相关疾病的发病机制,为相关疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9]。

参考文献:
1. Hu, Meng-Chun, Hsu, Hwei-Jan, Guo, Ing-Cherng, Chung, Bon-Chu. . Function of Cyp11a1 in animal models. In Molecular and cellular endocrinology, 215, 95-100. doi:. https://pubmed.ncbi.nlm.nih.gov/15026180/
2. Guo, Ing-Cherng, Hu, Meng-Chun, Chung, Bon-Chu. . Transcriptional regulation of CYP11A1. In Journal of biomedical science, 10, 593-8. doi:. https://pubmed.ncbi.nlm.nih.gov/14576461/
3. Muccee, Fatima, Bijou, Osama, Harakeh, Steve, Ansari, Mohammad Javed, Ghazanfar, Shakira. 2022. In-Silico Investigation of Effects of Single-Nucleotide Polymorphisms in PCOS-Associated CYP11A1 Gene on Mutated Proteins. In Genes, 13, . doi:10.3390/genes13071231. https://pubmed.ncbi.nlm.nih.gov/35886014/
4. Rytelewska, Edyta, Kisielewska, Katarzyna, Gudelska, Marlena, Kaminski, Tadeusz, Smolinska, Nina. 2019. The effect of orexin a on the StAR, CYP11A1 and HSD3B1 gene expression, as well as progesterone and androstenedione secretion in the porcine uterus during early pregnancy and the oestrous cycle. In Theriogenology, 143, 179-190. doi:10.1016/j.theriogenology.2019.10.012. https://pubmed.ncbi.nlm.nih.gov/31733930/
5. Zhang, Zhijun, Huang, Hongxin, Chen, Zetian, Xu, Zekuan, Li, Zheng. 2024. Helicobacter pylori promotes gastric cancer through CagA-mediated mitochondrial cholesterol accumulation by targeting CYP11A1 redistribution. In International journal of biological sciences, 20, 4007-4028. doi:10.7150/ijbs.96425. https://pubmed.ncbi.nlm.nih.gov/39113698/
6. Deng, Hong-Zhu, You, Cong, Xing, Yu, Chen, Kai-Yun, Zou, Xiao-Bing. 2015. A Family-Based Association Study of CYP11A1 and CYP11B1 Gene Polymorphisms With Autism in Chinese Trios. In Journal of child neurology, 31, 733-7. doi:10.1177/0883073815620672. https://pubmed.ncbi.nlm.nih.gov/26690694/
7. Rosal, Karen G, Chen, Wei-Yi, Chung, Bon-Chu. 2022. The A'-helix of CYP11A1 remodels mitochondrial cristae. In Journal of biomedical science, 29, 61. doi:10.1186/s12929-022-00846-7. https://pubmed.ncbi.nlm.nih.gov/35978408/
8. Alyousif, Sihad Salim Hakeem, Ozbakir, Burcu, Ozay, Ali Cenk, Tulay, Pinar. 2024. The association of CYP11A1 gene polymorphisms with the polycystic ovary syndrome patients. In Revista da Associacao Medica Brasileira (1992), 70, e20231293. doi:10.1590/1806-9282.20231293. https://pubmed.ncbi.nlm.nih.gov/39045925/
9. Guo, Ing-Cherng, Shih, Meng-Chun, Lan, Hsin-Chieh, Hu, Meng-Chun, Chung, Bon-Chu. 2007. Transcriptional regulation of human CYP11A1 in gonads and adrenals. In Journal of biomedical science, 14, 509-15. doi:. https://pubmed.ncbi.nlm.nih.gov/17594537/