Zdhhc7-flox Mouse
一般名
Zdhhc7-flox
製品ID
S-CKO-00256
背景情報
C57BL/6JCya
系統ID
CKOCMP-102193-Zdhhc7-B6J-VA
状況
このマウス系統を論文で使用する場合は、「Zdhhc7-flox Mouse（カタログ番号S-CKO-00256）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
標準的な配送方法では、少なくとも3匹のヘテロ接合体キャリアを保証しています。ホモ接合体キャリアや指定された性別の個体の繁殖サービスも利用可能です。
基本情報
系統名
Zdhhc7-flox
系統ID
CKOCMP-102193-Zdhhc7-B6J-VA
遺伝子名
製品ID
S-CKO-00256
遺伝子別名
Gramp2
遺伝子別名
C57BL/6JCya
NCBI ID
修正
Conditional knockout
染色体
Chr 8
表現型
アプリケーション
--
さらに
系統詳細
EnsemblトランスクリプトID
ENSMUST00000034280
NCBIトランスクリプトID
NM_133967
ターゲット領域
Exon 4
有効領域の大きさ
~1.0 kb
遺伝子研究の概要
Zdhhc7, encoding zinc finger DHHC-type palmitoyl transferase 7, is involved in protein S-palmitoylation, a reversible post-translational modification. It plays significant roles in multiple biological pathways, including those related to inflammation, autophagy, and cell cycle regulation. Genetic models, such as Zdhhc7 knockout (KO) mice, are valuable tools for studying its functions [1,2,4-6].
In the context of inflammation, Zdhhc7-mediated palmitoylation of NLRP3 at Cys126 promotes inflammasome activation. Zdhhc7 KO reduces NLRP3 activation in macrophages, highlighting its importance in this inflammatory process [1].
In autophagy, Zdhhc7-mediated S-palmitoylation of ATG16L1 at Cys153 facilitates LC3 lipidation and autophagosome formation. ATG16L1-KO HeLa cells with S-palmitoylation-deficient mutant ATG16L1C153S show defects in these processes [2].
Regarding cell cycle and cancer, Zdhhc7 inhibits the androgen receptor in prostate cancer cells. Zdhhc7 depletion increases the oncogenic properties of prostate cancer cells, while restoring it suppresses cell proliferation and invasion in vitro and in vivo [3].
In a mouse model of colitis, pharmacological inhibition of APT2 or knockout of Zdhhc7 relieves symptoms, as Zdhhc7-mediated palmitoylation of STAT3 promotes TH17 cell differentiation [4].
In pyroptosis, Zdhhc7-mediated palmitoylation of GSDMD on C192 is crucial for its cleavage and subsequent pyroptosis-related events. Perturbing this palmitoylation suppresses pyroptosis, affecting mouse survival in lipopolysaccharide-induced septic shock [5].
In brain development, deleting the Zdhhc7 gene in mice impairs fibre development, demonstrating its role in microstructural changes [6].
In ovarian clear cell carcinoma, suppression of Zdhhc7 enhances ferroptosis via YAP1 activation [7].
In hepatocellular carcinoma, increased Zdhhc7 abundance is associated with poor prognosis, and perturbing the positive feedback loop among DHHC7, STAT3, and HIF1α reduces tumor cell growth in vivo [8].
In an Alzheimer's disease mouse model, hippocampal silencing of Zdhhc7 prevents cognitive deficits [9].
In non-alcoholic steatohepatitis, KLF10 promotes the disease progression through transcriptional activation of Zdhhc7, which palmitoylates CD36 [10].
In conclusion, Zdhhc7 is essential for various biological functions mainly through protein S-palmitoylation. Studies using Zdhhc7 KO or related genetic models have revealed its significance in multiple disease areas, including inflammatory diseases, cancer, neurodegenerative diseases, and metabolic liver diseases, providing potential therapeutic targets for these conditions.
References：
1. Yu, Tao, Hou, Dan, Zhao, Jiaqi, Linder, Maurine E, Lin, Hening. 2024. NLRP3 Cys126 palmitoylation by ZDHHC7 promotes inflammasome activation. In Cell reports, 43, 114070. doi:10.1016/j.celrep.2024.114070. https://pubmed.ncbi.nlm.nih.gov/38583156/
2. Wei, Fujing, Wang, Yu, Yao, Jia, Kong, Eryan, Yang, Aimin. 2024. ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation. In Autophagy, 20, 2719-2737. doi:10.1080/15548627.2024.2386915. https://pubmed.ncbi.nlm.nih.gov/39087410/
3. Lin, Zhuoyuan, Agarwal, Shivani, Tan, Song, Zhao, Jonathan C, Yu, Jindan. 2023. Palmitoyl acyltransferase ZDHHC7 inhibits androgen receptor and suppresses prostate cancer. In Oncogene, 42, 2126-2138. doi:10.1038/s41388-023-02718-2. https://pubmed.ncbi.nlm.nih.gov/37198397/
4. Zhang, Mingming, Zhou, Lixing, Xu, Yuejie, Linder, Maurine E, Lin, Hening. 2020. A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis. In Nature, 586, 434-439. doi:10.1038/s41586-020-2799-2. https://pubmed.ncbi.nlm.nih.gov/33029007/
5. Zhang, Na, Zhang, Jian, Yang, Yuanxin, Tan, Li, Xu, Daichao. 2024. A palmitoylation-depalmitoylation relay spatiotemporally controls GSDMD activation in pyroptosis. In Nature cell biology, 26, 757-769. doi:10.1038/s41556-024-01397-9. https://pubmed.ncbi.nlm.nih.gov/38538834/
6. Kerkenberg, Nicole, Wachsmuth, Lydia, Zhang, Mingyue, Zhang, Weiqi, Hohoff, Christa. 2021. Brain microstructural changes in mice persist in adulthood and are modulated by the palmitoyl acyltransferase ZDHHC7. In The European journal of neuroscience, 54, 5951-5967. doi:10.1111/ejn.15415. https://pubmed.ncbi.nlm.nih.gov/34355442/
7. Furutake, Yoko, Yamaguchi, Ken, Yamanoi, Koji, Matsumura, Noriomi, Mandai, Masaki. . YAP1 Suppression by ZDHHC7 Is Associated with Ferroptosis Resistance and Poor Prognosis in Ovarian Clear Cell Carcinoma. In Molecular cancer therapeutics, 23, 1652-1665. doi:10.1158/1535-7163.MCT-24-0145. https://pubmed.ncbi.nlm.nih.gov/38958503/
8. Jiang, Yi, Xu, Yuejie, Zhu, Chengliang, Lin, Hening, Zhang, Mingming. 2023. STAT3 palmitoylation initiates a positive feedback loop that promotes the malignancy of hepatocellular carcinoma cells in mice. In Science signaling, 16, eadd2282. doi:10.1126/scisignal.add2282. https://pubmed.ncbi.nlm.nih.gov/38051779/
9. Natale, Francesca, Spinelli, Matteo, Rinaudo, Marco, Fusco, Salvatore, Grassi, Claudio. 2024. Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer's disease. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2402604121. doi:10.1073/pnas.2402604121. https://pubmed.ncbi.nlm.nih.gov/39589870/
10. Yang, Shu, Jia, Lijing, Xiang, Jiaqing, Liang, Zhen, Lu, Yan. 2022. KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7. In EMBO reports, 23, e54229. doi:10.15252/embr.202154229. https://pubmed.ncbi.nlm.nih.gov/35492028/
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