Cyp2d22-KO 基因敲除小鼠

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产品名称

Cyp2d22-KO 基因敲除小鼠

产品编号

S-KO-20548

品系全称

C57BL/6JCya-Cyp2d22em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-56448-Cyp2d22-B6J-VB

品系状态

使用本品系发表的文献需注明: Cyp2d22-KO 基因敲除小鼠 mice (Strain S-KO-20548) 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 2, subfamily d, polypeptide 22
基因别称
2D22
染色体号
Chr 15 (Mouse)
转录本 ID
NCBI: NM_001163472 | Ensembl: ENSMUST00000023083
修饰方式
全身性基因敲除
靶向范围
Exon 3~8
敲除长度
~2.5 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
Cyp2d22,也称为Cytochrome P450 2d22,是一种在哺乳动物中表达的细胞色素P450酶。细胞色素P450酶是一类重要的药物代谢酶,在药物代谢、激素合成和解毒过程中发挥着关键作用。Cyp2d22在药物代谢中具有重要作用,特别是与药物代谢和解毒过程相关。它在肝脏中表达较高,在肾上腺、卵巢和乳腺中也有表达。Cyp2d22的催化活性与人类CYP2D6类似,但两者在底物特异性和动力学特性上存在差异。此外,Cyp2d22在神经系统中也有表达,可能与神经退行性疾病的发生和发展有关。

在肝脏中,Cyp2d22的表达受到性别和激素的影响。研究发现,Cyp2d22的表达在雌性小鼠的动情周期中呈现周期性变化,在动情期达到峰值。此外,卵巢切除术和抗雌激素药物可以抑制Cyp2d22的表达,而雌激素和孕酮可以促进其表达。这些结果表明,性激素在Cyp2d22的调节中发挥重要作用,并可能影响药物的代谢和毒性。

Cyp2d22在神经系统中也有表达,可能与神经退行性疾病的发生和发展有关。研究发现,Cyp2d22在多巴胺能神经元的损伤中发挥保护作用。在农药引起的帕金森病模型中,Cyp2d22的表达降低,而白藜芦醇可以部分恢复Cyp2d22的表达和活性,从而减轻神经退行性病变。此外,尼古丁也可以通过上调Cyp2d22的表达和活性来保护多巴胺能神经元。这些结果表明,Cyp2d22在神经退行性疾病中发挥重要的保护作用。

Cyp2d22的表达和活性受到多种因素的调节。研究发现,人工细胞外基质可以影响Cyp2d22的表达。在PVLA上培养的肝细胞中,Cyp2d22的表达在培养3天后恢复,而在胶原和E-cad-Fc上培养的肝细胞中,Cyp2d22的表达随着时间的推移而显著降低。此外,Cyp2d22的表达还受到生长因子和炎症因子的影响。这些结果表明,Cyp2d22的表达和活性受到多种因素的调节,并可能影响药物的代谢和毒性。

Cyp2d22在药物代谢和神经退行性疾病中发挥重要作用。Cyp2d22的表达和活性受到性别、激素、细胞外基质、生长因子和炎症因子等多种因素的调节。Cyp2d22的研究有助于深入理解药物代谢和神经退行性疾病的发病机制,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Konstandi, Maria, Andriopoulou, Christina E, Cheng, Jie, Gonzalez, Frank J. . Sex steroid hormones differentially regulate CYP2D in female wild-type and CYP2D6-humanized mice. In The Journal of endocrinology, 245, 301-314. doi:10.1530/JOE-19-0561. https://pubmed.ncbi.nlm.nih.gov/32171179/
2. Rasheed, Mohd Sami Ur, Tripathi, Manish Kumar, Patel, Devendra Kumar, Singh, Mahendra Pratap. . Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-Induced Parkinsonism. In Protein and peptide letters, 27, 1038-1045. doi:10.2174/0929866527666200403110036. https://pubmed.ncbi.nlm.nih.gov/32242774/
3. Srivastava, Garima, Dixit, Anubhuti, Yadav, Sharawan, Prakash, Om, Singh, Mahendra Pratap. 2012. Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. In Free radical biology & medicine, 52, 1294-306. doi:10.1016/j.freeradbiomed.2012.02.005. https://pubmed.ncbi.nlm.nih.gov/22334051/
4. Blume, N, Leonard, J, Xu, Z J, Remotti, H, Fishman, J. . Characterization of Cyp2d22, a novel cytochrome P450 expressed in mouse mammary cells. In Archives of biochemistry and biophysics, 381, 191-204. doi:. https://pubmed.ncbi.nlm.nih.gov/11032406/
5. Yu, Ai-Ming, Haining, Robert L. 2006. Expression, purification, and characterization of mouse CYP2d22. In Drug metabolism and disposition: the biological fate of chemicals, 34, 1167-74. doi:. https://pubmed.ncbi.nlm.nih.gov/16595712/
6. Adachi, Tatsuhiko, Goto, Mitsuaki, Cho, Chong-Su, Akaike, Toshihiro. 2011. Modulation of cytochrome P450 gene expression in primary hepatocytes on various artificial extracellular matrices. In Biochemical and biophysical research communications, 413, 577-81. doi:10.1016/j.bbrc.2011.09.004. https://pubmed.ncbi.nlm.nih.gov/21930114/
7. Singh, Seema, Singh, Kavita, Patel, Devendra Kumar, Singh, Raj Kumar, Singh, Mahendra Pratap. . The expression of CYP2D22, an ortholog of human CYP2D6, in mouse striatum and its modulation in 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease phenotype and nicotine-mediated neuroprotection. In Rejuvenation research, 12, 185-97. doi:10.1089/rej.2009.0850. https://pubmed.ncbi.nlm.nih.gov/19594327/
8. Sarwar, Md Shahid, Cheng, David, Peter, Rebecca Mary, Hart, Ronald P, Kong, Ah-Ng. 2023. Metabolic rewiring and epigenetic reprogramming in leptin receptor-deficient db/db diabetic nephropathy mice. In European journal of pharmacology, 953, 175866. doi:10.1016/j.ejphar.2023.175866. https://pubmed.ncbi.nlm.nih.gov/37331680/
9. Koh, Kwi Hye, Xie, Hui, Yu, Ai-Ming, Jeong, Hyunyoung. 2010. Altered cytochrome P450 expression in mice during pregnancy. In Drug metabolism and disposition: the biological fate of chemicals, 39, 165-9. doi:10.1124/dmd.110.035790. https://pubmed.ncbi.nlm.nih.gov/20971892/
10. McLaughlin, Lesley A, Dickmann, Leslie J, Wolf, C Roland, Henderson, Colin J. 2008. Functional expression and comparative characterization of nine murine cytochromes P450 by fluorescent inhibition screening. In Drug metabolism and disposition: the biological fate of chemicals, 36, 1322-31. doi:10.1124/dmd.108.021261. https://pubmed.ncbi.nlm.nih.gov/18420780/