Chd4-flox 基因敲除小鼠

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产品名称

Chd4-flox 基因敲除小鼠

产品编号

S-CKO-00616

品系全称

C57BL/6JCya-Chd4em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-107932-Chd4-B6J-VA

品系状态

使用本品系发表的文献需注明: Chd4-flox 基因敲除小鼠 mice (Strain S-CKO-00616) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
chromodomain helicase DNA binding protein 4
基因别称
9530019N15Rik,D6Ertd380e,Mi-2beta,mKIAA4075
染色体号
Chr 6 (Mouse)
转录本 ID
NCBI: NM_001346610 | Ensembl: ENSMUST00000056889
修饰方式
条件性基因敲除
靶向范围
Exon 3~10
敲除长度
~3.2 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:1344380Mice homozygous for a gene trapped allele exhibit embryonic lethality between E3.5 and E4.5, absent blastocoele failure of trophectoderm function and increased apoptosis in blastocysts.
Chd4,也称为Chromodomain helicase DNA-binding protein 4,是染色质重塑和去乙酰化酶复合物(NuRD)的催化核心。NuRD复合物通过调节染色质可及性来抑制基因转录,在多种生物学过程中发挥重要作用,包括细胞分化、发育、代谢和疾病发生。

Chd4在多种疾病中发挥重要作用,包括胃癌、糖尿病、心血管疾病和癌症。在胃癌中,Chd4的表达与化疗耐药性相关。Chd4通过激活MEK/ERK信号通路促进胃癌细胞的增殖和化疗耐药性[1]。在糖尿病中,Chd4的表达与葡萄糖稳态和胰岛素分泌相关。Chd4缺失导致β细胞功能障碍和葡萄糖不耐受[2]。在心血管疾病中,Chd4的表达与心脏发育和心律失常相关。Chd4缺失导致心肌细胞分化和心脏发育异常,增加心律失常的风险[3,4,5]。在癌症中,Chd4的表达与癌症进展和免疫浸润相关。Chd4通过调节补体基因表达和CD8 T细胞浸润在肝癌中发挥致癌作用[6]。此外,Chd4的表达还与红细胞发育和胎儿血红蛋白表达相关。Chd4缺失导致胎儿血红蛋白基因表达增加[7]。Chd4的表达还与生殖细胞发育和精子发生相关。Chd4缺失导致精子发生停滞和精子数量减少[8]。此外,Chd4的表达还与免疫细胞功能和T细胞活化相关。Chd4缺失导致抗原呈递细胞活性降低和T细胞活化受损[9]。

综上所述,Chd4是一种重要的染色质重塑因子,参与调节基因转录和生物学过程。Chd4在多种疾病中发挥重要作用,包括胃癌、糖尿病、心血管疾病和癌症。Chd4的研究有助于深入理解染色质重塑的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Wu, Jing, Zhou, Zhijun, Li, Jin, Liu, Mingyang, Zhang, Changhua. 2022. CHD4 promotes acquired chemoresistance and tumor progression by activating the MEK/ERK axis. In Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 66, 100913. doi:10.1016/j.drup.2022.100913. https://pubmed.ncbi.nlm.nih.gov/36603431/
2. Davidson, Rebecca K, Kanojia, Sukrati, Wu, Wenting, Sims, Emily K, Spaeth, Jason M. . The Chd4 Helicase Regulates Chromatin Accessibility and Gene Expression Critical for β-Cell Function In Vivo. In Diabetes, 72, 746-757. doi:10.2337/db22-0939. https://pubmed.ncbi.nlm.nih.gov/36913741/
3. . 2017. Prevalence and architecture of de novo mutations in developmental disorders. In Nature, 542, 433-438. doi:10.1038/nature21062. https://pubmed.ncbi.nlm.nih.gov/28135719/
4. Robbe, Zachary L, Shi, Wei, Wasson, Lauren K, Davis, Ian J, Conlon, Frank L. 2022. CHD4 is recruited by GATA4 and NKX2-5 to repress noncardiac gene programs in the developing heart. In Genes & development, 36, 468-482. doi:10.1101/gad.349154.121. https://pubmed.ncbi.nlm.nih.gov/35450884/
5. Sweat, Mason E, Shi, Wei, Keating, Erin M, Conlon, Frank L, Pu, William T. 2024. CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.12.04.626894. https://pubmed.ncbi.nlm.nih.gov/39677667/
6. Shi, Wei, Wasson, Lauren K, Dorr, Kerry M, Seidman, Jonathan G, Conlon, Frank L. 2024. CHD4 and SMYD1 repress common transcriptional programs in the developing heart. In Development (Cambridge, England), 151, . doi:10.1242/dev.202505. https://pubmed.ncbi.nlm.nih.gov/38619323/
7. Shao, Simin, Cao, Haowei, Wang, Zhongkun, Xia, Dian, Zhang, Daoyong. 2020. CHD4/NuRD complex regulates complement gene expression and correlates with CD8 T cell infiltration in human hepatocellular carcinoma. In Clinical epigenetics, 12, 31. doi:10.1186/s13148-020-00827-3. https://pubmed.ncbi.nlm.nih.gov/32070428/
8. Lan, Xianjiang, Ren, Ren, Feng, Ruopeng, Shi, Junwei, Blobel, Gerd A. 2020. ZNF410 Uniquely Activates the NuRD Component CHD4 to Silence Fetal Hemoglobin Expression. In Molecular cell, 81, 239-254.e8. doi:10.1016/j.molcel.2020.11.006. https://pubmed.ncbi.nlm.nih.gov/33301730/
9. de Castro, Rodrigo O, Carbajal, Agustin, Previato de Almeida, Luciana, Griffin, Courtney T, Pezza, Roberto J. 2022. Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development. In Epigenetics & chromatin, 15, 16. doi:10.1186/s13072-022-00448-5. https://pubmed.ncbi.nlm.nih.gov/35568926/