Crebbp-flox 基因敲除小鼠

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产品名称

Crebbp-flox 基因敲除小鼠

产品编号

S-CKO-01858

品系全称

C57BL/6JCya-Crebbpem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-12914-Crebbp-B6J-VA

品系状态

使用本品系发表的文献需注明: Crebbp-flox 基因敲除小鼠 mice (Strain S-CKO-01858) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型
Notch信号通路
TGF-β信号通路
Wnt信号通路
JAK-STAT信号通路

基本信息

基因研究概述

质控标准

基因
基因全称
CREB binding protein
基因别称
CBP,CBP/p300,KAT3A,p300/CBP
染色体号
Chr 16 (Mouse)
转录本 ID
NCBI: NM_001025432 | Ensembl: ENSMUST00000023165
修饰方式
条件性基因敲除
靶向范围
Exon 4
敲除长度
~1.2 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:1098280Homozygotes for null or altered alleles die around midgestation with defects in hemopoiesis, blood vessel formation, and neural tube closure. Heterozygotes may exhibit skeletal, cardiac, and hematopoietic defects, retarded growth, and hematologic tumors.
CREBBP,也称为CREB结合蛋白,是一种重要的转录共激活因子和组蛋白乙酰转移酶。它参与调节细胞内的多种事件,包括基因表达、细胞周期、细胞分化、发育和代谢等。CREBBP与另一个蛋白质EP300形成复合物,共同调节基因的转录和表达。CREBBP在多种疾病中发挥重要作用,包括癌症、遗传性疾病和代谢性疾病等。

在癌症中,CREBBP的突变或表达异常与多种肿瘤的发生和发展有关。例如,在小细胞肺癌中,CREBBP的失活可以导致肿瘤的发生,并增加对组蛋白去乙酰化酶(HDAC)抑制剂的敏感性[5]。在急性髓系白血病中,CREBBP和EP300作为重要的表观遗传调控因子,通过多种机制参与白血病的发生和发展[4]。此外,在前列腺癌中,CREBBP和EP300的抑制剂可以抑制肿瘤细胞的生长和迁移,并可能具有潜在的治疗价值[2]。

在遗传性疾病中,CREBBP的突变与多种遗传性疾病的发生有关。例如,CREBBP的突变可以导致Rubinstein-Taybi综合征,这是一种罕见的常染色体显性遗传病,患者的主要特征为颅面畸形、骨骼畸形、生长延迟和精神及运动发育迟缓[1][3][8][9]。此外,CREBBP的基因多态性与弥漫性大B细胞淋巴瘤的易感性和预后相关[7]。

在代谢性疾病中,CREBBP也发挥重要作用。例如,CREBBP相关的转录过程与2型糖尿病的发病机制相关[6]。

综上所述,CREBBP是一种重要的转录共激活因子和组蛋白乙酰转移酶,参与调节细胞内的多种事件,包括基因表达、细胞周期、细胞分化、发育和代谢等。CREBBP在多种疾病中发挥重要作用,包括癌症、遗传性疾病和代谢性疾病等。通过对CREBBP的研究,可以深入理解细胞内事件的调节机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Shen, Jie, Zhao, Mingyi, Zeng, Zhihui, He, Wei, Chen, Chunyuan. . CREBBP gene mutation in an infant with Rubinstein-Taybi syndrome. In Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 45, 198-203. doi:10.11817/j.issn.1672-7347.2020.180770. https://pubmed.ncbi.nlm.nih.gov/32386048/
2. Furlan, Tobias, Kirchmair, Alexander, Sampson, Natalie, Handle, Florian, Culig, Zoran. 2021. MYC-Mediated Ribosomal Gene Expression Sensitizes Enzalutamide-resistant Prostate Cancer Cells to EP300/CREBBP Inhibitors. In The American journal of pathology, 191, 1094-1107. doi:10.1016/j.ajpath.2021.02.017. https://pubmed.ncbi.nlm.nih.gov/33705753/
3. Zhang, Jiangwei, Wang, Changyan, Li, Ming, Qiu, Zhengqing. . [CREBBP gene mutation in two boys with Rubinstein-Taybi syndrome]. In Zhonghua er ke za zhi = Chinese journal of pediatrics, 52, 673-7. doi:. https://pubmed.ncbi.nlm.nih.gov/25476429/
4. Wu, Wenqi, Jiang, Yanan, Xing, Donghui, Ren, Guibing, Zhao, Zhigang. 2024. The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia. In Cell death discovery, 10, 206. doi:10.1038/s41420-024-01940-5. https://pubmed.ncbi.nlm.nih.gov/38693103/
5. Jia, Deshui, Augert, Arnaud, Kim, Dong-Wook, Park, Kwon-Sik, MacPherson, David. 2018. Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition. In Cancer discovery, 8, 1422-1437. doi:10.1158/2159-8290.CD-18-0385. https://pubmed.ncbi.nlm.nih.gov/30181244/
6. Morris, Andrew P, Voight, Benjamin F, Teslovich, Tanya M, Boehnke, Michael, McCarthy, Mark I. 2012. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. In Nature genetics, 44, 981-90. doi:10.1038/ng.2383. https://pubmed.ncbi.nlm.nih.gov/22885922/
7. Zhao, Haifeng, Kan, Yutian, Wang, Xinyuan, Ge, Peng, Qian, Zhengzi. 2019. Genetic polymorphism and transcriptional regulation of CREBBP gene in patient with diffuse large B-cell lymphoma. In Bioscience reports, 39, . doi:10.1042/BSR20191162. https://pubmed.ncbi.nlm.nih.gov/31366566/
8. Al-Qattan, Mohammad M, Rahbeeni, Zuhair A, Al-Hassnan, Zuhair N, Mahabbat, Nehal, Alsufayan, Faris A S. 2020. Chromosome 16p13.3 Contiguous Gene Deletion Syndrome including the SLX4, DNASE1, TRAP1, and CREBBP Genes Presenting as a Relatively Mild Rubinstein-Taybi Syndrome Phenotype: A Case Report of a Saudi Boy. In Case reports in genetics, 2020, 6143050. doi:10.1155/2020/6143050. https://pubmed.ncbi.nlm.nih.gov/32181026/
9. Snehi, Sagarika, Kaur, Anupriya, Chaudhry, Chakshu, Kaushik, Sushmita. 2023. Congenital glaucoma as a presenting feature of Rubinstein-Taybi syndrome in an infant with a novel pathogenic variant in the CREBBP gene. In BMJ case reports, 16, . doi:10.1136/bcr-2022-251543. https://pubmed.ncbi.nlm.nih.gov/36653044/