Dync2h1-flox 基因敲除小鼠

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产品名称

Dync2h1-flox 基因敲除小鼠

产品编号

S-CKO-00854

品系全称

C57BL/6JCya-Dync2h1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-110350-Dync2h1-B6J-VA

品系状态

使用本品系发表的文献需注明: Dync2h1-flox 基因敲除小鼠 mice (Strain S-CKO-00854) 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 cytoplasmic 2 heavy chain 1
基因别称
4432416O06Rik,D030010H02Rik,D330044F14Rik,DHC11,DHC1b,DHC2,Dnchc2,b2b414Clo,m152Asp,m407Asp,mDHC11
染色体号
Chr 9 (Mouse)
转录本 ID
NCBI: NM_029851.3 | Ensembl: ENSMUST00000048417
修饰方式
条件性基因敲除
靶向范围
Exon 18
敲除长度
~628 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:107736Homozygotes for a gene trap allele show complete embryonic lethality with altered heart looping and brain morphology. Chemically induced mutants show randomized heart looping and polydactyly. Holoprosencephaly or exencephaly, dorsoventral forebrain patterning defects, micrognathia, and cardiac, renal, airway and eye defects may be observed.
DYNC2H1基因,也称为动力蛋白细胞质2重链1,编码的是一种动力蛋白,这是一种在细胞内运输过程中起关键作用的分子马达蛋白。动力蛋白是一种复杂的蛋白质,它负责将细胞器、蛋白质和其他分子沿着细胞内的微管运输到正确的位置。DYNC2H1基因的变异与多种骨骼疾病有关,这些疾病统称为骨骼睫状体疾病(skeletal ciliopathies)。睫状体是细胞表面的一种细胞器,它们在细胞信号传导、细胞运动和细胞形态发生中发挥着重要作用。骨骼睫状体疾病通常由动力蛋白复合体中的基因突变引起,而DYNC2H1基因正是这个复合体的一部分。

DYNC2H1基因的变异与短肋胸廓发育不全3型(short-rib thoracic dysplasia 3 with or without polydactyly,SRTD3)有关,这是一种严重的胎儿骨骼发育不良,其特征是肢体缩短、胸廓狭窄,有时伴有并指或多指。SRTD3是一种常染色体隐性遗传疾病,由DYNC2H1基因的同源或复合杂合突变引起。DYNC2H1基因的变异会导致动力蛋白复合体的功能受损,从而影响细胞内的运输过程,最终导致骨骼发育异常。

DYNC2H1基因的变异也与窒息性胸廓发育不全(asphyxiating thoracic dysplasia,ATD)有关,这是一种以胸廓狭窄和肺功能受损为特征的骨骼疾病。DYNC2H1基因的变异会影响动力蛋白复合体的功能,从而导致细胞内运输过程受损,最终导致胸廓狭窄和肺功能受损。

DYNC2H1基因的变异还与其他骨骼疾病有关,例如埃利斯的范克里夫德综合征(Ellis-van Creveld syndrome,EvC)。EvC是一种以多指、短肋、胸廓狭窄和牙齿发育不良为特征的骨骼疾病。DYNC2H1基因的变异会影响动力蛋白复合体的功能,从而导致细胞内运输过程受损,最终导致EvC的发生。

除了骨骼疾病,DYNC2H1基因的变异还与其他疾病有关,例如舌部错构瘤。舌部错构瘤是一种良性的舌部肿瘤,其病因尚不清楚。DYNC2H1基因的变异会影响动力蛋白复合体的功能,从而导致细胞内运输过程受损,最终导致舌部错构瘤的发生。

综上所述,DYNC2H1基因编码的动力蛋白在细胞内运输过程中起关键作用,DYNC2H1基因的变异与多种骨骼疾病和其他疾病有关。这些疾病的发生机制可能与动力蛋白复合体的功能受损有关。未来研究需要进一步探索DYNC2H1基因变异导致疾病的具体机制,为这些疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8]。

参考文献:
1. Chen, Wenqi, Li, Yazhou, Zhang, Jing, Liang, Ying, Guo, Qing. 2023. Genetic variations in the DYNC2H1 gene causing SRTD3 (short-rib thoracic dysplasia 3 with or without polydactyly). In Frontiers in genetics, 14, 1125473. doi:10.3389/fgene.2023.1125473. https://pubmed.ncbi.nlm.nih.gov/37091781/
2. Zhang, Wenjuan, Taylor, S Paige, Ennis, Hayley A, Krakow, Deborah, Cohn, Daniel H. 2017. Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies. In Human mutation, 39, 152-166. doi:10.1002/humu.23362. https://pubmed.ncbi.nlm.nih.gov/29068549/
3. Piceci-Sparascio, Francesca, Micale, Lucia, Torres, Barbara, Castori, Marco, De Luca, Alessandro. 2023. Clinical variability in DYNC2H1-related skeletal ciliopathies includes Ellis-van Creveld syndrome. In European journal of human genetics : EJHG, 31, 479-484. doi:10.1038/s41431-022-01276-7. https://pubmed.ncbi.nlm.nih.gov/36599940/
4. Zhao, Wenquan, Ye, Guanchen, Li, Qi, Yu, Mengfei, Wang, Huiming. 2022. Pathogenic variant of DYNC2H1 associated with lingual hamartoma in a Chinese pedigree. In Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 51, 755-761. doi:10.1111/jop.13339. https://pubmed.ncbi.nlm.nih.gov/36087272/
5. Čechová, Anna, Baxová, Alice, Zeman, Jiří, Čunát, Václav, Tesařová, Markéta. . Attenuated Type of Asphyxiating Thoracic Dysplasia due to Mutations in DYNC2H1 Gene. In Prague medical report, 120, 124-130. doi:10.14712/23362936.2019.17. https://pubmed.ncbi.nlm.nih.gov/31935347/
6. Geng, Kaiyue, Mu, Kai, Zhao, Yan, Cui, Yazhou, Han, Jinxiang. . Identification of novel compound heterozygous mutations of the DYNC2H1 gene in a fetus with short-rib thoracic dysplasia 3 with or without polydactyly. In Intractable & rare diseases research, 9, 95-98. doi:10.5582/irdr.2020.01031. https://pubmed.ncbi.nlm.nih.gov/32494556/
7. Fang, Yuying, Li, Shuo, Yu, Dongyi. 2023. Genetic analysis and prenatal diagnosis of short-rib thoracic dysplasia 3 with or without polydactyly caused by compound heterozygous variants of DYNC2H1 gene in four Chinese families. In Frontiers in genetics, 14, 1075187. doi:10.3389/fgene.2023.1075187. https://pubmed.ncbi.nlm.nih.gov/37007936/
8. Deng, Linbei, Cheung, Sau Wai, Schmitt, Eric S, Chen, Lei, Sun, Luming. 2018. Targeted gene panel sequencing prenatally detects two novel mutations of DYNC2H1 in a fetus with increased biparietal diameter and polyhydramnios. In Birth defects research, 110, 364-371. doi:10.1002/bdr2.1146. https://pubmed.ncbi.nlm.nih.gov/29359448/