Ppp1r12a-KO 基因敲除小鼠

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产品名称

Ppp1r12a-KO 基因敲除小鼠

产品编号

S-KO-19309

品系全称

C57BL/6JCya-Ppp1r12aem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-17931-Ppp1r12a-B6J-VA

品系状态

使用本品系发表的文献需注明: Ppp1r12a-KO 基因敲除小鼠 mice (Strain S-KO-19309) 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
protein phosphatase 1, regulatory subunit 12A
基因别称
1200015F06Rik,5730577I22Rik,D10Ertd625e,Mypt1
染色体号
Chr 10 (Mouse)
转录本 ID
NCBI: NM_001368736 | Ensembl: ENSMUST00000219263
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:1309528Homozygous null mice die before E7.5. Mice homozygous for a smooth muscle specific conditional knockout exhibit altered intestinal smooth muscle contractility.
PPP1R12A基因编码的蛋白称为肌球蛋白轻链磷酸酶目标亚基1(MYPT1),它是肌球蛋白轻链磷酸酶(MLCP)蛋白复合物的一个关键组成部分。MLCP负责调节平滑肌收缩和舒张,从而影响血压的维持。PPP1R12A基因具有32个外显子,并且通过选择性剪接产生多种转录本,这些转录本在循环系统的细胞中表达,包括人脐静脉内皮细胞(HUVEC)、人隐静脉平滑肌细胞(HSVSMC)和血小板。这些细胞类型表达多达10种转录本,其中HUVECs和HSVSMCs主要表达全长变体,而血小板主要表达跳过E14和E13外显子的变体。

PPP1R12A基因在多种生物学过程中发挥重要作用,包括细胞迁移、细胞粘附、形态发生和基因表达调控。此外,PPP1R12A基因的表达与多种疾病相关,包括前列腺癌、乳腺癌、结直肠癌和妊娠高血压。在前列腺癌中,PPP1R12A基因的表达与患者的预后相关,高表达PPP1R12A的患者预后较差。在乳腺癌中,PPP1R12A基因的表达与YAP的激活相关,YAP是一种转录共激活因子,对多种癌症的恶性程度至关重要。在结直肠癌中,PPP1R12A基因的拷贝数与患者的预后相关,低拷贝数PPP1R12A的患者预后较差。在妊娠高血压中,PPP1R12A基因的SNV与疾病的发生相关,其中rs11114256和rs2694657与叠加性先兆子痫(SPE)的发生相关。

PPP1R12A基因的突变也与多种先天性畸形相关,包括生殖泌尿和/或脑畸形综合征(GUBS)、中脑畸形和尿生殖畸形。PPP1R12A基因的缺失功能突变会导致GUBS的发生,这是一种涉及神经或泌尿生殖系统异常的综合征。PPP1R12A基因的突变也与中脑畸形和尿生殖畸形相关,这些畸形与生殖系统发育异常有关。

综上所述,PPP1R12A基因编码的MYPT1蛋白在调节平滑肌收缩和舒张、细胞迁移、细胞粘附、形态发生和基因表达调控中发挥重要作用。PPP1R12A基因的表达与多种疾病相关,包括前列腺癌、乳腺癌、结直肠癌和妊娠高血压。PPP1R12A基因的突变也与多种先天性畸形相关,包括GUBS、中脑畸形和尿生殖畸形。PPP1R12A基因的研究有助于深入理解其在生物学和疾病中的作用,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Zou, Zhihao, Liu, Ren, Liang, Yingke, Zhong, Weide, Liang, Yuxiang. 2021. Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer. In Frontiers in genetics, 12, 703210. doi:10.3389/fgene.2021.703210. https://pubmed.ncbi.nlm.nih.gov/34484299/
2. Saldanha, Paulo André, Bolanle, Israel Olapeju, Palmer, Timothy Martin, Nikitenko, Leonid Leonidovich, Rivero, Francisco. 2022. Complex Transcriptional Profiles of the PPP1R12A Gene in Cells of the Circulatory System as Revealed by In Silico Analysis and Reverse Transcription PCR. In Cells, 11, . doi:10.3390/cells11152315. https://pubmed.ncbi.nlm.nih.gov/35954160/
3. Inoue, Chiaki, Mukai, Kojiro, Matsudaira, Tatsuyuki, Uchida, Yasunori, Taguchi, Tomohiko. 2023. PPP1R12A is a recycling endosomal phosphatase that facilitates YAP activation. In Scientific reports, 13, 19740. doi:10.1038/s41598-023-47138-0. https://pubmed.ncbi.nlm.nih.gov/37957190/
4. Kono, Ai, Shinya, Kaori, Nakayama, Tomohiro, Yamamoto, Tatsuo, Kawana, Kei. 2021. Haplotype-based, case-control study of myosin phosphatase target subunit 1 (PPP1R12A) gene and hypertensive disorders of pregnancy. In Hypertension in pregnancy, 40, 88-96. doi:10.1080/10641955.2021.1872613. https://pubmed.ncbi.nlm.nih.gov/33459569/
5. Zhang, Chenbo, Li, Ajian, Li, Huaguang, Yin, Lu, Li, Jianwen. 2015. PPP1R12A Copy Number Is Associated with Clinical Outcomes of Stage III CRC Receiving Oxaliplatin-Based Chemotherapy. In Mediators of inflammation, 2015, 417184. doi:10.1155/2015/417184. https://pubmed.ncbi.nlm.nih.gov/26113782/
6. Diao, Yanxia, Sun, Weiwei, Zhang, Zhen, Zhao, Bing, Chen, Xin. 2023. Clinical report and genetic analysis of a neonate with genitourinary and/or brain malformation syndrome caused by a non-coding sequence variant of PPP1R12A. In Molecular genetics & genomic medicine, 11, e2223. doi:10.1002/mgg3.2223. https://pubmed.ncbi.nlm.nih.gov/37272772/
7. Kiss, Andrea, Erdődi, Ferenc, Lontay, Beáta. 2018. Myosin phosphatase: Unexpected functions of a long-known enzyme. In Biochimica et biophysica acta. Molecular cell research, 1866, 2-15. doi:10.1016/j.bbamcr.2018.07.023. https://pubmed.ncbi.nlm.nih.gov/30076859/
8. Hughes, Joel J, Alkhunaizi, Ebba, Kruszka, Paul, Muenke, Maximilian, Chitayat, David. 2019. Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations. In American journal of human genetics, 106, 121-128. doi:10.1016/j.ajhg.2019.12.004. https://pubmed.ncbi.nlm.nih.gov/31883643/
9. Frew, Edward, Sainty, Rebecca, Chappell-Maor, Louise, Lartey, Jon, Monk, David. 2024. Differential expression of PPP1R12A transcripts, including those harbouring alternatively spliced micro-exons, in placentae from complicated pregnancies. In Placenta, 151, 1-9. doi:10.1016/j.placenta.2024.04.005. https://pubmed.ncbi.nlm.nih.gov/38615553/
10. Picard, Jean-Yves, Morin, Gilles, Devouassoux-Shisheboran, Mojgan, Bole, Christine, Josso, Nathalie. . Persistent Müllerian duct syndrome associated with genetic defects in the regulatory subunit of myosin phosphatase. In Human reproduction (Oxford, England), 37, 2952-2959. doi:10.1093/humrep/deac239. https://pubmed.ncbi.nlm.nih.gov/36331510/