Slc25a13-KO 基因敲除小鼠

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产品名称

Slc25a13-KO 基因敲除小鼠

产品编号

S-KO-10229

品系全称

C57BL/6JCya-Slc25a13em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-50799-Slc25a13-B6J-VA

品系状态

使用本品系发表的文献需注明: Slc25a13-KO 基因敲除小鼠 mice (Strain S-KO-10229) 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
solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 13
基因别称
Ctrn
染色体号
Chr 6 (Mouse)
转录本 ID
NCBI: NM_015829 | Ensembl: ENSMUST00000015256
修饰方式
全身性基因敲除
靶向范围
Exon 3
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:1354721Mice homozygous for disruptions in this gene appear normal, healthy and fertile, although they have a number of metabolic defects, but the spontaneous hyperspin deletion spanning from intron 3 to exon 17 also eliminates a modifier of Dlx5 causing a recessive vestibular and mortality phenotype
SLC25A13,也称为citrin,是一种重要的线粒体天冬氨酸/谷氨酸载体蛋白。它在肝细胞中发挥着关键作用,负责将细胞质中的天冬氨酸转运到线粒体基质中,同时将线粒体基质中的谷氨酸转运到细胞质中,从而参与氨基酸代谢和能量代谢。SLC25A13的突变会导致citrin缺陷症(CD),这是一种常染色体隐性遗传病,患者会出现肝功能异常、高氨血症、意识障碍等症状。CD的表型与年龄有关,新生儿期表现为新生儿肝内胆汁淤积(NICCD),而成年期则表现为成年型Ⅱ型高瓜氨酸血症(CTLN2)[1,2,3,4,5,6,7,8,9,10]。

SLC25A13基因的突变会导致其编码的citrin蛋白功能异常,从而影响氨基酸代谢和能量代谢。CD患者由于代谢补偿,从儿童到成年期通常表现健康,但由于饮食偏好(不喜欢高碳水化合物食物,喜欢脂肪和蛋白质丰富的食物),如果摄入过多的碳水化合物或酒精,可能会突然发病,出现高氨血症和意识障碍等症状。CD患者的肝脏也可能出现脂肪肝,这可能与肝脏中的脂肪酸代谢和氧化以及甘油三酯的分泌有关[1]。因此,CD患者需要进行营养治疗,包括使用中链甘油三酯油和钠丙酮酸等药物来预防高氨血症[1]。

SLC25A13基因的突变具有明显的地理分布特征,例如,在中国,北方人群的SLC25A13等位基因异质性比南方人群高[2]。此外,SLC25A13基因的突变谱系也在不断扩大,研究人员已经发现了许多新的突变,包括错义突变、无义突变、剪接位突变、缺失突变和插入突变等[2,3,4,7]。这些发现为CD的分子诊断和遗传咨询提供了重要的参考价值。

SLC25A13基因的启动子区域也受到了研究人员的关注,通过生物信息学和功能分析,研究人员发现SLC25A13基因的启动子区域缺乏TATA盒和典型的启动子元件,但包含CCAAT盒和两个GC盒[6]。此外,研究人员还发现SLC25A13基因的转录本具有显著的多样性,包括28种替代剪接变体(ASV)和2种异常转录本[9]。这些发现为CD的分子诊断和基因治疗提供了新的思路。

综上所述,SLC25A13是一种重要的线粒体天冬氨酸/谷氨酸载体蛋白,其突变会导致citrin缺陷症(CD),这是一种常染色体隐性遗传病,患者会出现肝功能异常、高氨血症、意识障碍等症状。CD的表型与年龄有关,新生儿期表现为新生儿肝内胆汁淤积(NICCD),而成年期则表现为成年型Ⅱ型高瓜氨酸血症(CTLN2)。SLC25A13基因的突变具有明显的地理分布特征,突变谱系也在不断扩大。SLC25A13基因的启动子区域和转录本具有显著的多样性,为CD的分子诊断和基因治疗提供了新的思路。

参考文献:
1. Komatsu, Michiharu, Tanaka, Naoki, Kimura, Takefumi, Yazaki, Masahide. 2023. Citrin Deficiency: Clinical and Nutritional Features. In Nutrients, 15, . doi:10.3390/nu15102284. https://pubmed.ncbi.nlm.nih.gov/37242166/
2. Lin, Wei-Xia, Zeng, Han-Shi, Zhang, Zhan-Hui, Wen, Wang-Rong, Song, Yuan-Zong. 2016. Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution. In Scientific reports, 6, 29732. doi:10.1038/srep29732. https://pubmed.ncbi.nlm.nih.gov/27405544/
3. Sachs, Nimrod, Wechsberg, Oded, Landau, Yuval E, Lidzbarsky, Gabriel, Orenstein, Naama. 2023. A novel SLC25A13 gene splice site variant causes Citrin deficiency in an infant. In Gene, 874, 147483. doi:10.1016/j.gene.2023.147483. https://pubmed.ncbi.nlm.nih.gov/37196891/
4. Nguyen, Mai-Huong Thi, Nguyen, Anh-Hoa Pham, Ngo, Diem-Ngoc, Nguyen, Hoai-Nghia, Tran, Minh-Dien. 2023. The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis. In Journal of human genetics, 68, 305-312. doi:10.1038/s10038-022-01112-2. https://pubmed.ncbi.nlm.nih.gov/36599957/
5. Chang, Kuei-Wen, Chen, Huey-Ling, Chien, Yin-Hsiu, Chen, Tse-Ching, Yeh, Chau-Ting. 2011. SLC25A13 gene mutations in Taiwanese patients with non-viral hepatocellular carcinoma. In Molecular genetics and metabolism, 103, 293-6. doi:10.1016/j.ymgme.2011.03.013. https://pubmed.ncbi.nlm.nih.gov/21470889/
6. Chen, Jun-Lin, Zhang, Zhan-Hui, Li, Bing-Xiao, Cai, Zhen, Zhou, Qing-Hua. 2019. Bioinformatic and functional analysis of promoter region of human SLC25A13 gene. In Gene, 693, 69-75. doi:10.1016/j.gene.2019.01.023. https://pubmed.ncbi.nlm.nih.gov/30708027/
7. Song, Yuan-Zong, Zhang, Zhan-Hui, Lin, Wei-Xia, Kobayashi, Keiko, Saheki, Takeyori. 2013. SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China. In PloS one, 8, e74544. doi:10.1371/journal.pone.0074544. https://pubmed.ncbi.nlm.nih.gov/24069319/
8. Men, Shuai, Liu, Shuang, Zheng, Qin, Tang, Xinxin, Wang, Leilei. 2023. Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China. In Molecular genetics & genomic medicine, 11, e2152. doi:10.1002/mgg3.2152. https://pubmed.ncbi.nlm.nih.gov/36787440/
9. Zhang, Zhan-Hui, Lin, Wei-Xia, Deng, Mei, Zhao, Xin-Jing, Song, Yuan-Zong. 2012. Molecular analysis of SLC25A13 gene in human peripheral blood lymphocytes: Marked transcript diversity, and the feasibility of cDNA cloning as a diagnostic tool for citrin deficiency. In Gene, 511, 227-34. doi:10.1016/j.gene.2012.09.049. https://pubmed.ncbi.nlm.nih.gov/23022256/
10. Zhang, Linlin, Li, Yingying, Shi, Wenli, Cui, Shihong, Zhang, Xiaoan. 2019. Identification of a novel splicing mutation in the SLC25A13 gene from a patient with NICCD: a case report. In BMC pediatrics, 19, 348. doi:10.1186/s12887-019-1751-9. https://pubmed.ncbi.nlm.nih.gov/31607264/