Dnah8-flox 基因敲除小鼠

下单100%中奖,最高可得千元京东卡
复苏/繁育服务
产品名称

Dnah8-flox 基因敲除小鼠

产品编号

S-CKO-02063

品系全称

C57BL/6JCya-Dnah8em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-13417-Dnah8-B6J-VA

品系状态

使用本品系发表的文献需注明: Dnah8-flox 基因敲除小鼠 mice (Strain S-CKO-02063) 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
dynein, axonemal, heavy chain 8
基因别称
ATPase,Dnahc8,Hst6.7b,P1-Loop
染色体号
Chr 17 (Mouse)
转录本 ID
NCBI: NM_013811.3 | Ensembl: ENSMUST00000236140
修饰方式
条件性基因敲除
靶向范围
Exon 26
敲除长度
~687 bp
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:107714Mice homozygous for a null allele exhibit male infertility due to sperm immobility and malformed and/or absent flagella.
DNAH8,也称为动力蛋白轴丝重链8,是一种编码动力蛋白轴丝重链的基因。动力蛋白是一种微管依赖性马达蛋白,在细胞骨架的组装和细胞器的运动中发挥重要作用。DNAH8基因位于人类染色体6q21.2上,主要在睾丸和前列腺中表达。DNAH8编码的动力蛋白轴丝重链是精子鞭毛的重要组成部分,对精子的运动和形态至关重要。

DNAH8基因突变与多种男性不育相关疾病有关。其中,最常见的是弱畸精子症,这是一种精子活力和形态异常导致的不育症。研究发现,DNAH8基因的复合杂合突变可能导致精子鞭毛的多形性异常,进而导致弱畸精子症[1,3,4,5]。此外,DNAH8基因突变还与尿道下裂有关,尿道下裂是一种男性生殖器官发育异常,表现为尿道开口异常。研究发现,DNAH8基因的罕见有害变异在尿道下裂患者中显著富集[2,6]。DNAH8基因突变还与支气管扩张和原发性纤毛运动障碍有关,这两种疾病都与纤毛功能障碍有关[8,9]。

DNAH8基因突变导致的男性不育可能与多种机制有关。研究发现,DNAH8基因突变可能导致精子鞭毛的动力蛋白轴丝重链表达减少或缺失,进而导致精子鞭毛形态异常和运动能力下降[1,3,4,5]。此外,DNAH8基因突变还可能影响雄激素受体活性,进而影响精子的形成和发育[7]。DNAH8基因突变还可能影响纤毛的形态和功能,进而影响精子的运动和形态[8,9]。

综上所述,DNAH8基因突变与多种男性不育相关疾病有关,包括弱畸精子症、尿道下裂、支气管扩张和原发性纤毛运动障碍。DNAH8基因突变可能通过多种机制影响精子的形成和发育,进而导致男性不育。深入研究DNAH8基因的生物学功能和突变机制,有助于揭示男性不育的发病机制,为男性不育的诊断和治疗提供新的思路和策略。

参考文献:
1. Weng, Mingxiang, Sha, Yanwei, Zeng, Y U, Zhang, Xinzong, Zhou, Huiliang. . Mutations in DNAH8 contribute to multiple morphological abnormalities of sperm flagella and male infertility. In Acta biochimica et biophysica Sinica, 53, 472-480. doi:10.1093/abbs/gmab013. https://pubmed.ncbi.nlm.nih.gov/33704367/
2. Chen, Zhongzhong, Lei, Yunping, Finnell, Richard H, Xie, Hua, Chen, Fang. 2023. Whole-exome sequencing study of hypospadias. In iScience, 26, 106663. doi:10.1016/j.isci.2023.106663. https://pubmed.ncbi.nlm.nih.gov/37168556/
3. Yang, Yihong, Jiang, Chuan, Zhang, Xueguang, Liu, Hongqian, Shen, Ying. 2020. Loss-of-function mutation in DNAH8 induces asthenoteratospermia associated with multiple morphological abnormalities of the sperm flagella. In Clinical genetics, 98, 396-401. doi:10.1111/cge.13815. https://pubmed.ncbi.nlm.nih.gov/32681648/
4. Dil, Sobia, Khan, Asad, Unar, Ahsanullah, Bai, Shun, Shi, Qing-Hua. . A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family. In Asian journal of andrology, 25, 350-355. doi:10.4103/aja202274. https://pubmed.ncbi.nlm.nih.gov/36308074/
5. Liu, Chunyu, Miyata, Haruhiko, Gao, Yang, Zhang, Feng, Ikawa, Masahito. 2020. Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility. In American journal of human genetics, 107, 330-341. doi:10.1016/j.ajhg.2020.06.004. https://pubmed.ncbi.nlm.nih.gov/32619401/
6. Ding, Yu, Chen, Zu-Quan, Pan, Wen-Feng, Chen, Zhong-Zhong, Chen, Fang. 2024. The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias. In Asian journal of andrology, 26, 356-365. doi:10.4103/aja202377. https://pubmed.ncbi.nlm.nih.gov/38563741/
7. Wang, Yu, Ledet, Russell J, Imberg-Kazdan, Keren, Logan, Susan K, Garabedian, Michael J. . Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression. In Oncotarget, 7, 49268-49280. doi:10.18632/oncotarget.10284. https://pubmed.ncbi.nlm.nih.gov/27363033/
8. Staar, Ben O, Hegermann, Jan, Auber, Bernd, Wetzke, Martin, Ringshausen, Felix C. 2023. Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype. In Cells, 12, . doi:10.3390/cells12222651. https://pubmed.ncbi.nlm.nih.gov/37998386/
9. Zhou, Haiyan, Yin, Zhaochu, Ni, Bin, Luo, Shuwei, Xie, Wanqin. 2024. Whole exome sequencing analysis of 167 men with primary infertility. In BMC medical genomics, 17, 230. doi:10.1186/s12920-024-02005-3. https://pubmed.ncbi.nlm.nih.gov/39267058/