Hacd2-KO 基因敲除小鼠

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产品名称

Hacd2-KO 基因敲除小鼠

产品编号

S-KO-13418

品系全称

C57BL/6JCya-Hacd2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-70757-Hacd2-B6J-VA

品系状态

使用本品系发表的文献需注明: Hacd2-KO 基因敲除小鼠 mice (Strain S-KO-13418) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
3-hydroxyacyl-CoA dehydratase 2
基因别称
6330408J20Rik,Hcad2,Ptplb
染色体号
Chr 16 (Mouse)
转录本 ID
NCBI: NM_023587 | Ensembl: ENSMUST00000061156
修饰方式
全身性基因敲除
靶向范围
Exon 2
敲除长度
~0.9 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:1918007Homozygotes for a knock-out allele die around E9.5 and show developmental arrest, cardiovascular defects, altered mitochondrial function and structure, and accumulation of oxidized cardiolipin. Homozygotes for a hypomorphic allele die within 1-4 weeks of life from sudden growth arrest followed by cachexia and lethargy, and show hypoglycemia, hyperlactatemia, and impaired mitochondrial efficiency in the kidney and liver.
HACD2,也称为3-羟基酰基辅酶A脱水酶2,是一种重要的酶,参与长链脂肪酸(C ≥ 18)的合成。该基因编码的酶在细胞内脂肪酸的合成中发挥着关键作用,特别是在线粒体中。线粒体是细胞内的能量工厂,负责产生细胞所需的能量分子——三磷酸腺苷(ATP)。HACD2的表达在胚胎和出生后的发育过程中广泛存在,并在多个组织中发挥作用,包括肝脏、肌肉和脂肪组织。

根据多篇研究,HACD2的缺失在动物模型中会导致严重的后果。例如,在小鼠中,HACD2的缺失会导致早期死亡和线粒体疾病。具体来说,HACD2的缺失会导致线粒体功能障碍、氧化应激增加和能量代谢受损。这些变化会导致生长停滞、消瘦和活动减少,最终导致死亡。这些研究表明,HACD2对于维持线粒体功能和能量代谢至关重要。

除了在能量代谢中的作用,HACD2还与肥胖和代谢性疾病有关。研究发现,HACD2的缺失可以抵抗饮食诱导的肥胖和葡萄糖不耐受。HACD2的缺失会导致肝脏中脂肪酸合成和延伸的减少,从而降低脂肪积累和改善代谢指标。此外,HACD2的缺失还可以增加能量消耗,通过上调与产热相关的基因的表达。这些结果表明,HACD2可能是一个有潜力的治疗肥胖和相关代谢性疾病的靶点。

除了在哺乳动物中的作用,HACD2还在昆虫中发挥重要作用。研究发现,HACD2的缺失会影响昆虫的表皮渗透性和温度适应性。在一种全球性害虫——菜青虫(Plutella xylostella)中,HACD2的缺失会导致表皮渗透性增加,从而降低昆虫的存活率和繁殖能力。这表明HACD2对于昆虫的表皮形成和热适应至关重要。

此外,HACD2还与胰腺癌的发生和发展有关。研究发现,HACD2在胰腺癌细胞中高表达,并与患者的预后相关。HACD2通过增强PKM2从PRKN中的解离,影响糖酵解途径,从而促进胰腺癌细胞的增殖。这些结果表明,HACD2可能是一个有潜力的治疗胰腺癌的靶点。

综上所述,HACD2是一个重要的基因,参与脂肪酸合成和能量代谢。HACD2的缺失会导致线粒体功能障碍、肥胖和代谢性疾病、表皮渗透性改变和胰腺癌的发生和发展。HACD2的研究不仅有助于深入理解脂肪酸代谢的生物学功能和疾病发生机制,还为疾病的治疗和预防提供了新的思路和策略。

参考文献:
1. Khadhraoui, Nahed, Prola, Alexandre, Vandestienne, Aymeline, Tiret, Laurent, Pilot-Storck, Fanny. 2023. Hacd2 deficiency in mice leads to an early and lethal mitochondrial disease. In Molecular metabolism, 69, 101677. doi:10.1016/j.molmet.2023.101677. https://pubmed.ncbi.nlm.nih.gov/36693621/
2. Wei, Lengyun, Weng, Shengmei, Lu, Xuyang, Yang, Qin, Chen, Yong Q. 2022. 3-Hydroxyacyl-CoA dehydratase 2 deficiency confers resistance to diet-induced obesity and glucose intolerance. In Biochemical and biophysical research communications, 605, 134-140. doi:10.1016/j.bbrc.2022.03.057. https://pubmed.ncbi.nlm.nih.gov/35325655/
3. Lei, Gaoke, Zhou, Huiling, Chen, Yanting, You, Minsheng, You, Shijun. 2023. A very long-chain fatty acid enzyme gene, PxHacd2 affects the temperature adaptability of a cosmopolitan insect by altering epidermal permeability. In The Science of the total environment, 891, 164372. doi:10.1016/j.scitotenv.2023.164372. https://pubmed.ncbi.nlm.nih.gov/37236474/
4. Jiang, Ping, Iqbal, Ambreen, Cui, Zhiqian, Yu, Haibin, Zhao, Zhihui. 2022. Bta-miR-33a affects gene expression and lipid levels in Chinese Holstein mammary epithelial cells. In Archives animal breeding, 65, 357-370. doi:10.5194/aab-65-357-2022. https://pubmed.ncbi.nlm.nih.gov/36304442/
5. Yu, Hengwei, Wang, Jianfang, Zhang, Ke, Mei, Chugang, Zan, Linsen. 2023. Integrated multi-omics analysis reveals variation in intramuscular fat among muscle locations of Qinchuan cattle. In BMC genomics, 24, 367. doi:10.1186/s12864-023-09452-9. https://pubmed.ncbi.nlm.nih.gov/37391702/
6. Chu, Xuanning, Zhao, Jinyu, Shen, Yuting, Ma, Lingman, Zhou, Yiran. 2025. HACD2 Promotes Pancreatic Cancer Progression by Enhancing PKM2 Dissociation From PRKN in a Dehydratase-Independent Manner. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), , e2407942. doi:10.1002/advs.202407942. https://pubmed.ncbi.nlm.nih.gov/39836601/
7. Kwok, Kelvin H M, Rydén, Mikael, Andersson, Daniel P, Arner, Peter, Dahlman, Ingrid. 2019. Prospective analyses of white adipose tissue gene expression in relation to long-term body weight changes. In International journal of obesity (2005), 44, 377-387. doi:10.1038/s41366-019-0385-1. https://pubmed.ncbi.nlm.nih.gov/31164724/
8. Du, Lili, Li, Keanning, Chang, Tianpeng, Li, Junya, Gao, Huijiang. 2022. Integrating genomics and transcriptomics to identify candidate genes for subcutaneous fat deposition in beef cattle. In Genomics, 114, 110406. doi:10.1016/j.ygeno.2022.110406. https://pubmed.ncbi.nlm.nih.gov/35709924/
9. Sawai, Megumi, Uchida, Yukiko, Ohno, Yusuke, Sassa, Takayuki, Kihara, Akio. 2017. The 3-hydroxyacyl-CoA dehydratases HACD1 and HACD2 exhibit functional redundancy and are active in a wide range of fatty acid elongation pathways. In The Journal of biological chemistry, 292, 15538-15551. doi:10.1074/jbc.M117.803171. https://pubmed.ncbi.nlm.nih.gov/28784662/
10. Lin, Ruiyi, Li, Huihuang, Lin, Weilong, Lai, Lianjie, Lin, Weimin. 2024. Whole-genome selection signature differences between Chaohu and Ji'an red ducks. In BMC genomics, 25, 522. doi:10.1186/s12864-024-10339-6. https://pubmed.ncbi.nlm.nih.gov/38802792/