Mettl3-flox Mouse
一般名
Mettl3-flox
製品ID
S-CKO-12035
背景情報
C57BL/6NCya
系統ID
CKOCMP-56335-Mettl3-B6N-VA
状況
このマウス系統を論文で使用する場合は、「Mettl3-flox Mouse（カタログ番号S-CKO-12035）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
Mettl3-flox
系統ID
CKOCMP-56335-Mettl3-B6N-VA
遺伝子名
製品ID
S-CKO-12035
遺伝子別名
M6A, Spo8, 2310024F18Rik
遺伝子別名
C57BL/6NCya
NCBI ID
修正
Conditional knockout
染色体
Chr 14
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
ENSMUST00000022767
NCBIトランスクリプトID
NM_019721
ターゲット領域
Exon 2~3
有効領域の大きさ
~1.7 kb
遺伝子研究の概要
METTL3, also known as methyltransferase-like 3, is the sole catalytic subunit of the methyltransferase complex that catalyzes N6-methyladenosine (m6A) modification, the most abundant mRNA modification. This modification is involved in multiple biological processes, including cell differentiation, development, and disease-related pathways such as immune regulation, cancer progression, and inflammatory responses [2].
In tumor-infiltrating myeloid cells (TIMs), myeloid deficiency of METTL3 attenuated tumor growth in mice. It was found that METTL3 mediated m6A modification on Jak1 mRNA, enhancing JAK1 protein translation and STAT3 phosphorylation, and lactate in the tumor microenvironment induced METTL3 upregulation via H3K18 lactylation [1]. In small cell lung cancer, METTL3 was highly expressed in chemoresistant cells, and its knockdown reversed chemoresistance. METTL3 promoted chemoresistance by inducing mitophagy through m6A-mediated degradation of DCP2 [3]. In breast cancer, METTL3 knockdown reduced m6A modification and stability of PD-L1 mRNA, and inhibition of METTL3 enhanced anti-tumor immunity [4]. In colorectal cancer, upregulated METTL3 promoted cancer cell proliferation and metastasis through activating the JAK1/STAT3 signaling pathway [5]. In papillary thyroid cancer, downregulation of METTL3 was correlated with poor prognosis, and METTL3 knockout-related studies showed its tumor-suppressor role via c-Rel/IL-8-mediated neutrophil infiltration [6]. In diabetic nephropathy, podocyte-conditional knockout of METTL3 alleviated podocyte injury and albuminuria, and METTL3 promoted podocyte injury through m6A-modification of TIMP2 [7].
In conclusion, METTL3-mediated m6A modification plays crucial roles in various biological processes and diseases. Studies using KO/CKO mouse models have revealed its functions in cancer, including promoting tumor growth, chemoresistance, and immune escape, as well as in diabetic nephropathy, highlighting its potential as a therapeutic target in these disease areas.
References：
1. Xiong, Jia, He, Jia, Zhu, Jun, Lai, Lihua, Wang, Qingqing. 2022. Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. In Molecular cell, 82, 1660-1677.e10. doi:10.1016/j.molcel.2022.02.033. https://pubmed.ncbi.nlm.nih.gov/35320754/
2. Zeng, Chengwu, Huang, Wanxu, Li, Yangqiu, Weng, Hengyou. 2020. Roles of METTL3 in cancer: mechanisms and therapeutic targeting. In Journal of hematology & oncology, 13, 117. doi:10.1186/s13045-020-00951-w. https://pubmed.ncbi.nlm.nih.gov/32854717/
3. Sun, Yueqin, Shen, Weitao, Hu, Shulu, Zhu, Weiliang, Zhang, Jian. 2023. METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy. In Journal of experimental & clinical cancer research : CR, 42, 65. doi:10.1186/s13046-023-02638-9. https://pubmed.ncbi.nlm.nih.gov/36932427/
4. Wan, Weijun, Ao, Xiang, Chen, Quan, Luo, Donglin, Xu, Xiang. 2022. METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer. In Molecular cancer, 21, 60. doi:10.1186/s12943-021-01447-y. https://pubmed.ncbi.nlm.nih.gov/35197058/
5. Sun, Yuechao, Gong, Weipeng, Zhang, Song. 2023. METTL3 promotes colorectal cancer progression through activating JAK1/STAT3 signaling pathway. In Cell death & disease, 14, 765. doi:10.1038/s41419-023-06287-w. https://pubmed.ncbi.nlm.nih.gov/38001065/
6. He, Jing, Zhou, Mingxia, Yin, Jie, Yin, Huiqing, He, Fucheng. 2021. METTL3 restrains papillary thyroid cancer progression via m6A/c-Rel/IL-8-mediated neutrophil infiltration. In Molecular therapy : the journal of the American Society of Gene Therapy, 29, 1821-1837. doi:10.1016/j.ymthe.2021.01.019. https://pubmed.ncbi.nlm.nih.gov/33484966/
7. Jiang, Ling, Liu, Xueqi, Hu, Xueru, Meng, Xiaoming, Wu, Yonggui. 2022. METTL3-mediated m6A modification of TIMP2 mRNA promotes podocyte injury in diabetic nephropathy. In Molecular therapy : the journal of the American Society of Gene Therapy, 30, 1721-1740. doi:10.1016/j.ymthe.2022.01.002. https://pubmed.ncbi.nlm.nih.gov/34995800/
品質管理基準
精子検査
凍結前の精子濃度を測定し、精子の生存能力の判定します。
凍結後の精子では、各バッチから1本の凍結保存された精子を選び出し、体外受精に使用します。
環境基準:
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グローバル由来:
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