Fancd2-flox Mouse
一般名
Fancd2-flox
製品ID
S-CKO-05592
背景情報
C57BL/6JCya
系統ID
CKOCMP-211651-Fancd2-B6J-VA
状況
このマウス系統を論文で使用する場合は、「Fancd2-flox Mouse（カタログ番号S-CKO-05592）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
Fancd2-flox
系統ID
CKOCMP-211651-Fancd2-B6J-VA
遺伝子名
製品ID
S-CKO-05592
遺伝子別名
FA4, FAD, FACD, FA-D2, FANCD, 2410150O07Rik
遺伝子別名
C57BL/6JCya
NCBI ID
修正
Conditional knockout
染色体
Chr 6
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
ENSMUST00000036340
NCBIトランスクリプトID
NM_001033244
ターゲット領域
Exon 4~7
有効領域の大きさ
~3.4 kb
遺伝子研究の概要
FANCD2, the Fanconi anemia group D2 protein, is a pivotal component of the Fanconi anemia (FA) signaling pathway, a key genomic maintenance pathway. This pathway is activated in response to replication stress, and FANCD2 plays crucial roles in multiple aspects of cellular life, especially in the cellular responses to DNA damage [3].
Phosphorylation of FANCD2 by CHK1 triggers its FBXL12-dependent proteasomal degradation, facilitating its clearance at stalled replication forks and promoting efficient DNA replication under replication stress conditions [1]. Defects in the FA pathway, including those related to FANCD2, lead to R-loop accumulation, which contributes to genomic instability. The splicing factor SRSF1 and FANCD2 interact physically to suppress R-loop formation via mRNA export regulation [2]. Also, FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination, as lack of this ubiquitination impairs FANCD2-dependent functions [4]. FANCD2-FANCI complex surveys DNA, binds to double-stranded DNA and stalls at single-stranded-double-stranded DNA junctions, identifying sites of DNA damage [5]. Monoubiquitination of FANCD2 and FANCI by the FA core complex is a key step in the FA pathway, and deubiquitination by the USP1-UAF1 complex is also critical for interstrand cross-link (ICL) repair [6,7]. In SHH medulloblastoma, FANCD2 is highly expressed, and its deficiency sensitizes the tumor cells to radiotherapy via ferroptosis [8]. A PP2A phosphatase complex dephosphorylates an inhibitory cluster in FANCD2, licensing its loading onto chromosomes in response to DNA damage [9]. In osteosarcoma, FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway [10].
In conclusion, FANCD2 is essential for DNA damage response, replication fork protection, and regulation of processes like R-loop formation, mitotic DNA synthesis, and ferroptosis. Studies related to FANCD2, including those using loss-of-function models, have enhanced our understanding of its role in diseases such as cancer, highlighting its potential as a therapeutic target in certain cancers like SHH medulloblastoma and osteosarcoma.
References：
1. Brunner, Andrä, Li, Qiuzhen, Fisicaro, Samuele, Orre, Lukas M, Sangfelt, Olle. 2023. FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress. In Molecular cell, 83, 3720-3739.e8. doi:10.1016/j.molcel.2023.07.026. https://pubmed.ncbi.nlm.nih.gov/37591242/
2. Olazabal-Herrero, Anne, He, Boxue, Kwon, Youngho, Sung, Patrick, Kupfer, Gary M. 2024. The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export. In Cell reports, 43, 113610. doi:10.1016/j.celrep.2023.113610. https://pubmed.ncbi.nlm.nih.gov/38165804/
3. Nepal, Manoj, Che, Raymond, Ma, Chi, Zhang, Jun, Fei, Peiwen. 2017. FANCD2 and DNA Damage. In International journal of molecular sciences, 18, . doi:10.3390/ijms18081804. https://pubmed.ncbi.nlm.nih.gov/28825622/
4. Leung, Wendy, Baxley, Ryan M, Traband, Emma, Shima, Naoko, Bielinsky, Anja-Katrin. 2023. FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination. In Cell reports, 42, 113523. doi:10.1016/j.celrep.2023.113523. https://pubmed.ncbi.nlm.nih.gov/38060446/
5. Alcón, Pablo, Kaczmarczyk, Artur P, Ray, Korak Kumar, Rueda, David S, Passmore, Lori A. 2024. FANCD2-FANCI surveys DNA and recognizes double- to single-stranded junctions. In Nature, 632, 1165-1173. doi:10.1038/s41586-024-07770-w. https://pubmed.ncbi.nlm.nih.gov/39085614/
6. Li, Landing, Tan, Winnie, Deans, Andrew J. . Structural insight into FANCI-FANCD2 monoubiquitination. In Essays in biochemistry, 64, 807-817. doi:10.1042/EBC20200001. https://pubmed.ncbi.nlm.nih.gov/32725171/
7. Lemonidis, Kimon, Arkinson, Connor, Rennie, Martin L, Walden, Helen. 2021. Mechanism, specificity, and function of FANCD2-FANCI ubiquitination and deubiquitination. In The FEBS journal, 289, 4811-4829. doi:10.1111/febs.16077. https://pubmed.ncbi.nlm.nih.gov/34137174/
8. Zhou, Hong, Wang, Yan-Xia, Wu, Min, Wang, Yan, Bian, Xiu-Wu. 2024. FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis. In The Journal of pathology, 262, 427-440. doi:10.1002/path.6245. https://pubmed.ncbi.nlm.nih.gov/38229567/
9. Yang, Di, Bai, Fengxiang, Lopez Martinez, David, Cao, Lily Jiaqi, Cohn, Martin A. 2024. PP2A licenses the FANCD2/FANCI complex for chromosome loading. In Cell reports, 43, 114971. doi:10.1016/j.celrep.2024.114971. https://pubmed.ncbi.nlm.nih.gov/39535917/
10. Li, Xujun, Liu, Jiangyi. 2023. FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma. In BMC cancer, 23, 179. doi:10.1186/s12885-023-10626-7. https://pubmed.ncbi.nlm.nih.gov/36814203/
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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。
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