Hspa12a-KO 基因敲除小鼠

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产品名称

Hspa12a-KO 基因敲除小鼠

产品编号

S-KO-14145

品系全称

C57BL/6JCya-Hspa12aem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-73442-Hspa12a-B6J-VA

品系状态

使用本品系发表的文献需注明: Hspa12a-KO 基因敲除小鼠 mice (Strain S-KO-14145) 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
heat shock protein 12A
基因别称
1700063D12Rik,D5Mgi40,Gm19925,mKIAA0417
染色体号
Chr 19 (Mouse)
转录本 ID
NCBI: NM_175199.3 | Ensembl: ENSMUST00000066285
修饰方式
全身性基因敲除
靶向范围
Exon 2~6
敲除长度
~7339 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:1920692Homozygous knockout affects glucose metabolism, reducing susceptibility to diet-induced obesity. It also reduces diet-induced damage to the liver through suppression of macrophage recruitment, increases LPS-induced liver damage and increases susceptibility to ischemic brain injury.
HSPA12A,也称为热休克蛋白A12A,是一种非典型的HSP70家族成员。HSP70家族是一类广泛存在于原核和真核生物中的分子伴侣蛋白,它们在蛋白质折叠、运输、降解和细胞应激反应等方面发挥着重要作用。HSPA12A作为HSP70家族的一员,其功能与细胞应激、代谢调节和肿瘤发生发展密切相关。

在肝脏缺血再灌注损伤(LI/R)中,HSPA12A的表达在肝细胞中下调。肝细胞特异性过表达HSPA12A能够减轻LI/R引起的肝功能损伤和死亡率[1]。HSPA12A通过抑制糖酵解介导的HMGB1乳酰化及其从肝细胞中的分泌,从而抑制巨噬细胞的趋化作用和炎症激活,最终保护肝脏免受LI/R损伤[1]。

在心肌缺血再灌注损伤(MI/R)中,HSPA12A在心肌细胞中的表达下调,并伴随有氧糖酵解通量的减少。HSPA12A的敲除加剧了MI/R诱导的有氧糖酵解下降、心肌细胞死亡和心脏功能障碍[2]。HSPA12A通过维持有氧糖酵解稳态和组蛋白H3的乳酰化,进而支持心肌细胞在缺氧/复氧(H/R)挑战下的存活,并减轻MI/R损伤[2]。

在肾脏缺血再灌注损伤(KI/R)中,HSPA12A的表达在肾小管上皮细胞(TEC)中下调。HSPA12A的敲除损害了TEC的增殖和肾脏功能恢复。HSPA12A通过直接与转录因子c-Myc相互作用,增强其核定位,上调与TEC增殖相关的目标基因的表达,从而促进TEC增殖和肾脏功能恢复[3]。

在结直肠癌(CRC)中,SRSF11诱导的HSPA12A的替代剪接增加了N-钙粘蛋白的表达,并促进了CRC的转移潜力[4]。HSPA12A通过与增殖细胞核抗原(PCNA)结合,促进其三聚化,进而促进肝细胞癌(HCC)的生长和血管生成[6]。

HSPA12A在血管生成中也发挥着重要作用。HSPA12A通过刺激p38/ERK-AP-1信号通路,促进血管生成,并对于心肌梗死后心脏功能的恢复至关重要[5]。此外,HSPA12A的不稳定化CD147可以抑制乳酸的排出和迁移,从而抑制人类肾细胞癌(RCC)的转移[8]。

HSPA12A的缺乏导致白脂肪组织的棕色化增加,这可能是通过促进M2巨噬细胞的极化实现的[10]。HSPA12A的缺乏通过抑制PGC1α介导的线粒体完整性,从而增加了局部麻醉剂布比卡因引起的肌毒性[7]。

HSPA12A基因的变异与胃癌和结直肠癌的发病风险降低相关[9]。HSPA12A的基因多态性与中国儿童Wilms瘤的易感性降低相关[4]。

综上所述,HSPA12A在多种生物学过程中发挥着重要作用,包括细胞应激、代谢调节、肿瘤发生发展和血管生成等。HSPA12A的研究对于深入理解其生物学功能和疾病发生机制具有重要意义,并为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Du, Shuya, Zhang, Xiaojin, Jia, Yunxiao, Ding, Zhengnian, Liu, Li. 2023. Hepatocyte HSPA12A inhibits macrophage chemotaxis and activation to attenuate liver ischemia/reperfusion injury via suppressing glycolysis-mediated HMGB1 lactylation and secretion of hepatocytes. In Theranostics, 13, 3856-3871. doi:10.7150/thno.82607. https://pubmed.ncbi.nlm.nih.gov/37441587/
2. Yu, Wansu, Kong, Qiuyue, Jiang, Surong, Ding, Zhengnian, Liu, Li. 2024. HSPA12A maintains aerobic glycolytic homeostasis and Histone3 lactylation in cardiomyocytes to attenuate myocardial ischemia/reperfusion injury. In JCI insight, 9, . doi:10.1172/jci.insight.169125. https://pubmed.ncbi.nlm.nih.gov/38421727/
3. Li, Yunfan, Min, Xinxu, Zhang, Xiaojin, Liu, Li, Ding, Zhengnian. 2024. HSPA12A promotes c-Myc lactylation-mediated proliferation of tubular epithelial cells to facilitate renal functional recovery from kidney ischemia/reperfusion injury. In Cellular and molecular life sciences : CMLS, 81, 404. doi:10.1007/s00018-024-05427-5. https://pubmed.ncbi.nlm.nih.gov/39277835/
4. Pan, Yao-Jie, Huo, Fu-Chun, Kang, Meng-Jie, Wu, Meng-Di, Pei, Dong-Sheng. . Alternative splicing of HSPA12A pre-RNA by SRSF11 contributes to metastasis potential of colorectal cancer. In Clinical and translational medicine, 12, e1113. doi:10.1002/ctm2.1113. https://pubmed.ncbi.nlm.nih.gov/36394206/
5. Li, Tingting, Wu, Jun, Yu, Wansu, Ding, Zhengnian, Liu, Li. 2022. HSPA12A Stimulates p38/ERK-AP-1 Signaling to Promote Angiogenesis and Is Required for Functional Recovery Postmyocardial Infarction. In Oxidative medicine and cellular longevity, 2022, 2333848. doi:10.1155/2022/2333848. https://pubmed.ncbi.nlm.nih.gov/35783189/
6. Cheng, Hao, Cao, Xiaofei, Min, Xinxu, Liu, Li, Ding, Zhengnian. 2020. Heat-Shock protein A12A is a novel PCNA-binding protein and promotes hepatocellular carcinoma growth. In The FEBS journal, 287, 5464-5477. doi:10.1111/febs.15276. https://pubmed.ncbi.nlm.nih.gov/32128976/
7. Mao, Qian, Yu, Wansu, Liu, Shijiang, Liu, Li, Ding, Zhengnian. 2021. Downregulation of HSPA12A underlies myotoxicity of local anesthetic agent bupivacaine through inhibiting PGC1α-mediated mitochondrial integrity. In Toxicology and applied pharmacology, 434, 115798. doi:10.1016/j.taap.2021.115798. https://pubmed.ncbi.nlm.nih.gov/34793778/
8. Min, Xinxu, Zhang, Xiaojin, Li, Yunfan, Liu, Li, Ding, Zhengnian. 2020. HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma. In Theranostics, 10, 8573-8590. doi:10.7150/thno.44321. https://pubmed.ncbi.nlm.nih.gov/32754264/
9. Su, Qinghua, Wang, Yuan, Zhao, Jun, Jin, Tianbo, Xu, Jinkai. 2015. Polymorphisms of PRLHR and HSPA12A and risk of gastric and colorectal cancer in the Chinese Han population. In BMC gastroenterology, 15, 107. doi:10.1186/s12876-015-0336-9. https://pubmed.ncbi.nlm.nih.gov/26302849/
10. Cheng, Hao, Qi, Tao, Zhang, Xiaojin, Liu, Li, Ding, Zhengnian. 2019. Deficiency of heat shock protein A12A promotes browning of white adipose tissues in mice. In Biochimica et biophysica acta. Molecular basis of disease, 1865, 1451-1459. doi:10.1016/j.bbadis.2019.02.017. https://pubmed.ncbi.nlm.nih.gov/30797958/