Pfas-flox 基因敲除小鼠

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产品名称

Pfas-flox 基因敲除小鼠

产品编号

S-CKO-07954

品系全称

C57BL/6JCya-Pfasem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-237823-Pfas-B6J-VA

品系状态

使用本品系发表的文献需注明: Pfas-flox 基因敲除小鼠 mice (Strain S-CKO-07954) 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
phosphoribosylformylglycinamidine synthase (FGAR amidotransferase)
基因别称
4432409B16Rik,FGAMS,FGAR-AT,FGARAT,Gm18,PURL,Sofa
染色体号
Chr 11 (Mouse)
转录本 ID
NCBI: NM_001159519 | Ensembl: ENSMUST00000021282
修饰方式
条件性基因敲除
靶向范围
Exon 4~9
敲除长度
~3.3 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:2684864Mice heterozygous for spontaneous or ENU-induced mutations exhibit craniofacial abnormalities, most notably a domed cranium and short snout, variable white belly spots and white tail tips, and a range of eye defects including microphthalmia and anophthalmia.
Pfas基因,即perfluoroalkyl substances(PFAS),是一类全氟化有机化合物,广泛用于工业和家庭产品中,如防污剂、不粘锅涂层、消防泡沫等。PFAS因其化学稳定性、耐热性和疏水性而被广泛使用,但它们在环境中的持久性和生物累积性引起了人们对它们潜在健康影响的关注。

PFAS对人体健康的影响是多方面的。它们可以干扰内分泌系统,影响甲状腺激素的合成和代谢,导致甲状腺功能紊乱[2]。此外,PFAS还与胰岛素敏感性和胰岛β细胞功能的变化相关,可能增加患糖尿病的风险[1]。在生殖健康方面,PFAS暴露可能与精子质量和生育能力下降有关[3]。

遗传因素可能影响个体对PFAS暴露的反应。例如,研究发现某些基因多态性与PFAS在胎盘的转移速率和出生结果相关[4]。此外,遗传背景也可能影响PFAS与胰岛素敏感性和胰岛β细胞功能之间的关系[1]。例如,与2型糖尿病相关的基因变异可能作为修饰因子,影响PFAS与胰岛素敏感性和胰岛β细胞功能之间的关联。

除了内分泌和生殖健康,PFAS还可能影响其他生物学过程。例如,研究发现PFAS可以激活先天免疫系统,通过AIM2炎症小体介导炎症反应[5]。此外,PFAS还可以影响肝脏中的基因表达,包括脂质代谢基因和药物代谢酶基因,这可能影响肝脏对PFAS和其他外源性化合物的清除[6,7,8,9]。

综上所述,PFAS是一类对人类健康具有潜在威胁的环境污染物。它们可以干扰内分泌系统、影响胰岛素敏感性和胰岛β细胞功能、影响生殖健康,并可能通过激活先天免疫系统和影响肝脏基因表达而影响其他生物学过程。遗传因素可能影响个体对PFAS暴露的反应。因此,需要进一步研究PFAS对人类健康的影响,并采取措施减少PFAS暴露,以保护公众健康。

参考文献:
1. Valvi, Damaskini, Christiani, David C, Coull, Brent, Weihe, Pal, Grandjean, Philippe. 2023. Gene-environment interactions in the associations of PFAS exposure with insulin sensitivity and beta-cell function in a Faroese cohort followed from birth to adulthood. In Environmental research, 226, 115600. doi:10.1016/j.envres.2023.115600. https://pubmed.ncbi.nlm.nih.gov/36868448/
2. Pearce, Elizabeth N. 2023. Endocrine Disruptors and Thyroid Health. In Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 30, 172-176. doi:10.1016/j.eprac.2023.11.002. https://pubmed.ncbi.nlm.nih.gov/37956907/
3. Maxwell, DruAnne L, Oluwayiose, Oladele A, Houle, Emily, Petriello, Michael C, Pilsner, J Richard. 2024. Mixtures of per- and polyfluoroalkyl substances (PFAS) alter sperm methylation and long-term reprogramming of offspring liver and fat transcriptome. In Environment international, 186, 108577. doi:10.1016/j.envint.2024.108577. https://pubmed.ncbi.nlm.nih.gov/38521043/
4. Gundacker, Claudia, Graf-Rohrmeister, Klaudia, Gencik, Martin, Weiß, Stefan, Uhl, Maria. 2021. Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study. In Frontiers in genetics, 12, 664946. doi:10.3389/fgene.2021.664946. https://pubmed.ncbi.nlm.nih.gov/34220941/
5. Wang, Li-Qiu, Liu, Tao, Yang, Shuai, Li, Chun-Wei, Cui, Jun. 2021. Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome. In Nature communications, 12, 2915. doi:10.1038/s41467-021-23201-0. https://pubmed.ncbi.nlm.nih.gov/34006824/
6. Marques, Emily, Pfohl, Marisa, Wei, Wei, Bothun, Geoffrey D, Slitt, Angela. 2022. Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes. In Toxicology and applied pharmacology, 442, 115991. doi:10.1016/j.taap.2022.115991. https://pubmed.ncbi.nlm.nih.gov/35337807/
7. Clark, Kendra L, Shukla, Mamta, George, Jitu W, Rowley, M Jordan, Davis, John S. . An environmentally relevant mixture of per- and polyfluoroalkyl substances (PFAS) impacts proliferation, steroid hormone synthesis, and gene transcription in primary human granulosa cells. In Toxicological sciences : an official journal of the Society of Toxicology, 200, 57-69. doi:10.1093/toxsci/kfae049. https://pubmed.ncbi.nlm.nih.gov/38603627/
8. Vujic, Ena, Ferguson, Stephen S, Brouwer, Kim L R. . Effects of PFAS on human liver transporters: implications for health outcomes. In Toxicological sciences : an official journal of the Society of Toxicology, 200, 213-227. doi:10.1093/toxsci/kfae061. https://pubmed.ncbi.nlm.nih.gov/38724241/
9. Solan, Megan E, Schackmuth, Bennett, Bruce, Erica D, Sayes, Christie M, Lavado, Ramon. 2023. Effects of short-chain per- and polyfluoroalkyl substances (PFAS) on toxicologically relevant gene expression profiles in a liver-on-a-chip model. In Environmental pollution (Barking, Essex : 1987), 337, 122610. doi:10.1016/j.envpol.2023.122610. https://pubmed.ncbi.nlm.nih.gov/37742859/