Ip6k1-KO 基因敲除小鼠

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产品名称

Ip6k1-KO 基因敲除小鼠

产品编号

S-KO-18803

品系全称

C57BL/6JCya-Ip6k1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-27399-Ip6k1-B6J-VA

品系状态

使用本品系发表的文献需注明: Ip6k1-KO 基因敲除小鼠 mice (Strain S-KO-18803) 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
inositol hexaphosphate kinase 1
基因别称
1200016D08Rik,Ihpk1,InsP6,InsP6k1,Itpk6
染色体号
Chr 9 (Mouse)
转录本 ID
NCBI: NM_013785 | Ensembl: ENSMUST00000035214
修饰方式
全身性基因敲除
靶向范围
Exon 3
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:1351633Homozygous mutation of this gene results in impaired glucose tolerance, decreased insulin levels, bilateral epididymal aspermia, and testicular degeneration in males. Homozygous KO also increases presynaptic neurotransmitter release in the hippocampus.
IP6K1,即肌醇六磷酸激酶1,是一种在哺乳动物细胞中发挥重要作用的酶。它催化肌醇六磷酸(IP6)向肌醇七磷酸(IP7)的转化,而IP7是一种高能信号分子,能够通过直接结合到目标蛋白或通过焦磷酸化蛋白丝氨酸残基来调节目标蛋白活性。IP6K1在细胞骨架重塑、运输、细胞迁移、代谢、基因表达、DNA修复和免疫等方面发挥着重要作用[1]。此外,IP6K1在癌症进展中也有一定的作用,例如在乳腺癌中,IP6K1的表达与较差的预后相关[4]。

IP6K1的缺失或抑制能够对多种生理过程产生积极的影响。例如,IP6K1的缺失可以保护小鼠免受年龄相关的体重增加、胰岛素抵抗和代谢功能障碍[3]。此外,抑制IP6K1可以增强宿主对细菌的杀伤能力,同时减少肺部中性粒细胞的积累,从而减少细菌性肺炎引起的肺部损伤[2]。IP6K1的缺失还可以减少细胞迁移和侵袭,从而保护小鼠免受呼吸道癌的侵袭[5]。此外,IP6K1的缺失还可以增强间充质干细胞(MSCs)的活力,并减少高脂饮食诱导的骨骼退化[6]。最后,IP6K1的缺失还可以影响精子的形成,导致不育[7]。

IP6K1还能够调节肌醇的合成。肌醇是一种重要的细胞代谢和信号通路成分,其合成受到IP6K1的负向调控[8]。此外,IP6K1还能够与脂解调节蛋白Perilipin1相互作用,从而调节脂肪的分解[9]。

综上所述,IP6K1是一种重要的酶,参与多种生理过程。IP6K1的缺失或抑制能够对多种生理过程产生积极的影响,包括代谢、免疫和癌症进展等。因此,IP6K1可能成为治疗多种疾病,如肥胖症、糖尿病和癌症的潜在靶点。

参考文献:
1. Chakkour, Mohamed, Greenberg, Miriam L. 2024. Insights into the roles of inositol hexakisphosphate kinase 1 (IP6K1) in mammalian cellular processes. In The Journal of biological chemistry, 300, 107116. doi:10.1016/j.jbc.2024.107116. https://pubmed.ncbi.nlm.nih.gov/38403246/
2. Hou, Qingming, Liu, Fei, Chakraborty, Anutosh, Xu, Yuanfu, Luo, Hongbo R. . Inhibition of IP6K1 suppresses neutrophil-mediated pulmonary damage in bacterial pneumonia. In Science translational medicine, 10, . doi:10.1126/scitranslmed.aal4045. https://pubmed.ncbi.nlm.nih.gov/29618559/
3. Ghoshal, Sarbani, Mukherjee, Sandip, Chakraborty, Molee, Haubner, Jake, Chakraborty, Anutosh. 2022. Whole Body Ip6k1 Deletion Protects Mice from Age-Induced Weight Gain, Insulin Resistance and Metabolic Dysfunction. In International journal of molecular sciences, 23, . doi:10.3390/ijms23042059. https://pubmed.ncbi.nlm.nih.gov/35216174/
4. Sandström, Josefine, Balian, Alien, Lockowandt, Rebecca, Pérez-Tenorio, Gizeh, Stål, Olle. 2021. IP6K2 predicts favorable clinical outcome of primary breast cancer. In Molecular and clinical oncology, 14, 94. doi:10.3892/mco.2021.2256. https://pubmed.ncbi.nlm.nih.gov/33767863/
5. Jadav, Rathan S, Kumar, Dharmika, Buwa, Natasha, Balasubramanian, Nagaraj, Bhandari, Rashna. 2016. Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice. In Cellular signalling, 28, 1124-36. doi:10.1016/j.cellsig.2016.04.011. https://pubmed.ncbi.nlm.nih.gov/27140681/
6. Boregowda, Siddaraju V, Ghoshal, Sarbani, Booker, Cori N, Chakraborty, Anutosh, Phinney, Donald G. 2017. IP6K1 Reduces Mesenchymal Stem/Stromal Cell Fitness and Potentiates High Fat Diet-Induced Skeletal Involution. In Stem cells (Dayton, Ohio), 35, 1973-1983. doi:10.1002/stem.2645. https://pubmed.ncbi.nlm.nih.gov/28577302/
7. Malla, Aushaq Bashir, Bhandari, Rashna. 2017. IP6K1 is essential for chromatoid body formation and temporal regulation of Tnp2 and Prm2 expression in mouse spermatids. In Journal of cell science, 130, 2854-2866. doi:10.1242/jcs.204966. https://pubmed.ncbi.nlm.nih.gov/28743739/
8. Yu, Wenxi, Ye, Cunqi, Greenberg, Miriam L. 2016. Inositol Hexakisphosphate Kinase 1 (IP6K1) Regulates Inositol Synthesis in Mammalian Cells. In The Journal of biological chemistry, 291, 10437-44. doi:10.1074/jbc.M116.714816. https://pubmed.ncbi.nlm.nih.gov/26953345/
9. Ghoshal, Sarbani, Tyagi, Richa, Zhu, Qingzhang, Chakraborty, Anutosh. 2016. Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis. In The international journal of biochemistry & cell biology, 78, 149-155. doi:10.1016/j.biocel.2016.06.018. https://pubmed.ncbi.nlm.nih.gov/27373682/