Gpt2-flox Mouse
一般名
Gpt2-flox
製品ID
S-CKO-00685
背景情報
C57BL/6JCya
系統ID
CKOCMP-108682-Gpt2-B6J-VA
状況
このマウス系統を論文で使用する場合は、「Gpt2-flox Mouse（カタログ番号S-CKO-00685）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
Gpt2-flox
系統ID
CKOCMP-108682-Gpt2-B6J-VA
遺伝子名
製品ID
S-CKO-00685
遺伝子別名
4631422C05Rik, ALT2
遺伝子別名
C57BL/6JCya
遺伝子正式名称
glutamic pyruvate transaminase (alanine aminotransferase) 2
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
ENSMUST00000034136
NCBIトランスクリプトID
NM_173866
ターゲット領域
Exon 4
有効領域の大きさ
~1.8 kb
遺伝子研究の概要
GPT2, also known as glutamate pyruvate transaminase 2, is a nuclear-encoded mitochondrial enzyme. It catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. This reaction is involved in glutamine catabolism and plays a role in replenishing tricarboxylic acid (TCA) cycle intermediates, thus being crucial for cellular metabolism [7].
In glioblastoma, hypoxia-inducible factor (HIF)-2 directly induces GPT2, promoting tumor growth. Genetic or pharmacological inhibition of GPT2 decreases cell growth and migration, and knockout of GPT2 in mice inhibits tumor growth [1]. In triple-negative breast cancer, GPT2 is up-regulated and promotes metastasis. Exosomal GPT2 derived from these cells activates BTRC to enhance metastasis, and GPT2 knockout reduces lung metastasis in mice [2]. In acute myeloid leukemia, IGF2BP2 regulates GPT2 in the glutamine metabolism pathways, and inhibiting IGF2BP2 shows anti-leukemia effects [3]. In the locus coeruleus, GPT2 deficiency in mice causes early neurodegeneration, with loss of tyrosine hydroxylase-positive neurons, abnormal action potentials, and microgliosis and astrogliosis [4]. In breast cancer, GPT2 promotes metastasis through the GABA-GABAA receptor-PKC-CREB signaling pathway, and GPT2 knockout reduces metastasis and prolongs survival in mice [5]. In triple-negative breast cancer, abrogating GPT2 decreases TCA cycle intermediates, impairs mTORC1 activity, and induces autophagy, resulting in decreased tumor growth in xenograft studies [6]. In lung adenocarcinoma, inhibition of GPT2 suppresses tumor growth and increases CD4 and CD8 expression, and shows enhanced antitumor immunity when combined with anti-PD-L1 [8].
In conclusion, GPT2 plays essential roles in various biological processes and disease conditions. Gene knockout mouse models have significantly contributed to understanding its role in cancer, neurodegeneration, and metabolic-related disorders, revealing its potential as a therapeutic target in these disease areas.
References：
1. Zhang, Bo, Chen, Yan, Bao, Lei, Luo, Weibo. 2022. GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth. In Cells, 11, . doi:10.3390/cells11162597. https://pubmed.ncbi.nlm.nih.gov/36010673/
2. Cui, Mingqing, Peng, Jiawei, Zhou, Yuanyuan, Wang, Xixi, Cui, Daxiang. 2023. Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC. In Thoracic cancer, 14, 2018-2025. doi:10.1111/1759-7714.14984. https://pubmed.ncbi.nlm.nih.gov/37287397/
3. Weng, Hengyou, Huang, Feng, Yu, Zhaojin, Huang, Huilin, Chen, Jianjun. 2022. The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia. In Cancer cell, 40, 1566-1582.e10. doi:10.1016/j.ccell.2022.10.004. https://pubmed.ncbi.nlm.nih.gov/36306790/
4. Baytas, Ozan, Kauer, Julie A, Morrow, Eric M. 2022. Loss of mitochondrial enzyme GPT2 causes early neurodegeneration in locus coeruleus. In Neurobiology of disease, 173, 105831. doi:10.1016/j.nbd.2022.105831. https://pubmed.ncbi.nlm.nih.gov/35908744/
5. Li, Na, Xu, Xiang, Liu, Dan, Li, Qun, Mi, Jun. 2023. The delta subunit of the GABAA receptor is necessary for the GPT2-promoted breast cancer metastasis. In Theranostics, 13, 1355-1369. doi:10.7150/thno.80544. https://pubmed.ncbi.nlm.nih.gov/36923530/
6. Mitra, Devina, Vega-Rubin-de-Celis, Silvia, Royla, Nadine, Müller-Decker, Karin, Wiemann, Stefan. 2021. Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy. In International journal of cancer, 148, 1993-2009. doi:10.1002/ijc.33456. https://pubmed.ncbi.nlm.nih.gov/33368291/
7. Ouyang, Qing, Kavanaugh, Brian C, Joesch-Cohen, Lena, Liu, Judy S, Morrow, Eric M. 2019. GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates. In Human genetics, 138, 1183-1200. doi:10.1007/s00439-019-02057-x. https://pubmed.ncbi.nlm.nih.gov/31471722/
8. Wang, Bolin, Pei, Jinli, Xu, Shengnan, Liu, Jie, Yu, Jinming. 2023. System analysis based on glutamine catabolic-related enzymes identifies GPT2 as a novel immunotherapy target for lung adenocarcinoma. In Computers in biology and medicine, 165, 107415. doi:10.1016/j.compbiomed.2023.107415. https://pubmed.ncbi.nlm.nih.gov/37657356/
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