Pdha2-flox 基因敲除小鼠

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产品名称

Pdha2-flox 基因敲除小鼠

产品编号

S-CKO-04221

品系全称

C57BL/6JCya-Pdha2em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-18598-Pdha2-B6J-VA

品系状态

使用本品系发表的文献需注明: Pdha2-flox 基因敲除小鼠 mice (Strain S-CKO-04221) 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
pyruvate dehydrogenase E1 alpha 2
基因别称
Pdhal
染色体号
Chr 3 (Mouse)
转录本 ID
NCBI: NM_008811.2 | Ensembl: ENSMUST00000057860
修饰方式
条件性基因敲除
靶向范围
Exon 1
敲除长度
~2252 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
Pdha2(Pyruvate Dehydrogenase Alpha 2)基因编码人体内E1α亚基,是丙酮酸脱氢酶复合体(PDC)的重要组成部分。PDC在细胞能量代谢中起着关键作用,催化丙酮酸转化为乙酰辅酶A,从而进入三羧酸循环。Pdha2基因位于人类4号染色体上,与位于X染色体上的Pdha1基因编码同种E1α亚基,但两者表达模式不同。Pdha1基因在全身组织均有表达,而Pdha2基因仅限于睾丸生殖细胞表达[1][5][8]。

研究发现,Pdha2基因的表达受到DNA甲基化等表观遗传机制的控制。在正常情况下,Pdha2基因的启动子区域高度甲基化,而在睾丸生殖细胞中,Pdha2基因编码区域的CpG岛发生去甲基化,导致基因表达激活[3][4][5]。此外,Pdha2基因的表达还与细胞内RNA聚合酶II的招募密切相关[3]。

Pdha2基因的异常表达与多种疾病相关。研究发现,Pdha2基因的突变或表达异常可能导致男性不育,如非梗阻性无精子症(NOA)。在NOA患者中,Pdha2基因的表达异常可能与精子发生过程中的能量代谢障碍有关[2][6][7]。此外,Pdha2基因的突变还可能导致复杂的指畸形和男性不育等表型[7]。

近年来,研究发现Pdha2基因的表达激活可能为丙酮酸脱氢酶复合体缺乏症(PDC缺乏症)的治疗提供新的思路。PDC缺乏症是一种罕见的遗传性疾病,由于PDC功能异常导致能量代谢障碍。研究发现,在PDC缺乏症患者中,Pdha2基因的表达异常激活,导致PDC的活性恢复,为PDC缺乏症的治疗提供了新的策略[1][5]。

综上所述,Pdha2基因在细胞能量代谢和男性不育等生物学过程中发挥重要作用。Pdha2基因的表达受到DNA甲基化等表观遗传机制的控制,其异常表达与多种疾病相关。深入研究Pdha2基因的表达调控机制和功能,有助于揭示相关疾病的发病机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Pinheiro, Ana, Silva, Maria João, Pavlu-Pereira, Hana, Tavares de Almeida, Isabel, Rivera, Isabel. 2016. Data supporting the co-expression of PDHA1 gene and of its paralogue PDHA2 in somatic cells of a family. In Data in brief, 9, 68-77. doi:10.1016/j.dib.2016.08.029. https://pubmed.ncbi.nlm.nih.gov/27656664/
2. Kherraf, Zine-Eddine, Cazin, Caroline, Bouker, Amine, Arnoult, Christophe, Ray, Pierre F. 2022. Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia. In American journal of human genetics, 109, 508-517. doi:10.1016/j.ajhg.2022.01.011. https://pubmed.ncbi.nlm.nih.gov/35172124/
3. Pinheiro, Ana, Nunes, Maria João, Milagre, Inês, de Almeida, Isabel Tavares, Rivera, Isabel. 2012. Demethylation of the coding region triggers the activation of the human testis-specific PDHA2 gene in somatic tissues. In PloS one, 7, e38076. doi:10.1371/journal.pone.0038076. https://pubmed.ncbi.nlm.nih.gov/22675509/
4. Pinheiro, Ana, Faustino, Inês, Silva, Maria João, de Almeida, Isabel Tavares, Rivera, Isabel. 2009. Human testis-specific PDHA2 gene: methylation status of a CpG island in the open reading frame correlates with transcriptional activity. In Molecular genetics and metabolism, 99, 425-30. doi:10.1016/j.ymgme.2009.11.002. https://pubmed.ncbi.nlm.nih.gov/20005141/
5. Pinheiro, Ana, Silva, Maria João, Pavlu-Pereira, Hana, Tavares de Almeida, Isabel, Rivera, Isabel. 2016. Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: Null mutations in the PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells. In Gene, 591, 417-24. doi:10.1016/j.gene.2016.06.041. https://pubmed.ncbi.nlm.nih.gov/27343776/
6. Omolaoye, Temidayo S, Omolaoye, Victor A, Kandasamy, Richard K, Hachim, Mahmood Yaseen, Du Plessis, Stefan S. 2022. Omics and Male Infertility: Highlighting the Application of Transcriptomic Data. In Life (Basel, Switzerland), 12, . doi:10.3390/life12020280. https://pubmed.ncbi.nlm.nih.gov/35207567/
7. Yıldırım, Yeşerin, Ouriachi, Toufik, Woehlbier, Ute, Malik, Sajid, Tolun, Aslıhan. 2018. Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with complex digit malformation and male infertility. In European journal of human genetics : EJHG, 26, 876-885. doi:10.1038/s41431-018-0121-7. https://pubmed.ncbi.nlm.nih.gov/29581481/
8. Pinheiro, Ana, Silva, Maria João, Graça, Inês, Tavares de Almeida, Isabel, Rivera, Isabel. 2012. Pyruvate dehydrogenase complex: mRNA and protein expression patterns of E1α subunit genes in human spermatogenesis. In Gene, 506, 173-8. doi:10.1016/j.gene.2012.06.068. https://pubmed.ncbi.nlm.nih.gov/22750801/