Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney

Isabel Rubio-Aliaga; Isabelle Frey; Michael Boll; David A. Groneberg; Hans M. Eichinger; Rudi Balling; Hannelore Daniel

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Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney

机译：小鼠中肽转运蛋白Pept2基因的靶向破坏定义了其在肾脏中的生理作用

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The peptide transporter PEPT2 mediates the cellular uptake of di- and tripeptides and selected drugs by proton-substrate cotransport across the plasma membrane. PEPT2 was functionally identified initially in the apical membrane of renal tubular cells but was later shown to be expressed in other tissues also. To investigate the physiological importance of PEPT2 and for a detailed analysis of the protein expression sites, we generated a Pept2 knockout mouse line in which the Pept2 gene was disrupted by insertion of a β-galactosidase gene under the control of the PEPT2 promoter. The Pept2?/? mice showed no obvious phenotypic abnormalities but also no adaptive upregulation in the expression level of related genes in the kidney. The importance of PEPT2 in the reabsorption of filtered dipeptides was demonstrated in knockout animals by significantly reduced renal accumulation of a fluorophore-labeled and a radiolabeled dipeptide after in vivo administration of the tracers. This indicates that PEPT2 is the main system responsible for tubular reabsorption of peptide-bound amino acids, although this does not lead to major changes in renal excretion of protein or free amino acids.

机译：肽转运蛋白PEPT2通过质子-底物共转运穿过质膜来介导二肽和三肽以及选定药物的细胞吸收。 PEPT2最初在肾小管细胞的顶膜中被功能鉴定，但后来证明在其他组织中也表达。为了研究PEPT2的生理重要性并详细分析蛋白质表达位点，我们生成了一个 Pept2 敲除小鼠品系，其中的 Pept2 基因被插入a破坏了。 β-半乳糖苷酶基因受PEPT2启动子的控制。 Pept2 ？/？小鼠无明显表型异常，但肾脏相关基因表达水平无适应性上调。在体内施用示踪剂后，通过显着减少肾脏的荧光团标记和放射性标记的二肽的积累，证明了PEPT2在过滤的二肽重吸收中的重要性。这表明PEPT2是负责肽结合氨基酸的肾小管重吸收的主要系统，尽管这不会导致蛋白质或游离氨基酸的肾脏排泄发生重大变化。 展开▼

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《Molecular and Cellular Biology》 |2003年第9期|共6页

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Isabel Rubio-Aliaga; Isabelle Frey; Michael Boll; David A. Groneberg; Hans M. Eichinger; Rudi Balling; Hannelore Daniel;
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中图分类细胞生物学;

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1. Role and Relevance of Peptide Transporter 2(PEPT2)in the Kidney and Choroid Plexus:In Vivo Studies with Glycylsarcosine in Wild-Type and PEPT2 Knockout Mice [J] . Scott M.Ocheltree, Hong Shen, Yongjun Hu, The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics . 2005,第1期

机译：肽转运蛋白2（PEPT2）在肾和脉络丛中的作用和相关性：糖基肌氨酸在野生型和PEPT2基因敲除小鼠体内的研究。

2. Targeted disruption of peptide transporter Pept1 gene in mice significantly reduces dipeptide absorption in intestine. [J] . Hu Y, Smith DE, Ma K, Molecular pharmaceutics . 2008,第6期

机译：小鼠中肽转运蛋白Pept1基因的靶向破坏显着降低了肠道中的二肽吸收。

3. Targeted disruption of guanylyl cyclase-Aatriuretic peptide receptor-A gene provokes renal fibrosis and remodeling in null mutant mice: role of proinflammatory cytokines. [J] . Das S, Au E, Krazit ST, Endocrinology . 2010,第12期

机译：鸟苷酰环化酶-A /利钠肽受体-A基因的靶向破坏会在无效突变小鼠中引起肾脏纤维化和重塑：促炎细胞因子的作用。

4. ROLE OF PEPT2 IN PEPTIDE/MIMETIC TRAFFICKING AT THE BLOOD-CSF BARRIER [C] . David E. Smith Proceedings of the 29th Annual Meeting of the Controlled Release Society . 2002

机译：PEPT2在血液CSF屏障中在肽/隐性交易中的作用

5. Distinct roles for MEKK2 and MEKK3 in cell signaling, gene regulation and development as defined by targeted gene disruption. [D] . Lobel-Rice, Katherine Elizabeth. 2002

机译：MEKK2和MEKK3在细胞信号传导，基因调控和发育中的不同作用，如靶向基因破坏所定义。

6. Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney [O] . Isabel Rubio-Aliaga, Isabelle Frey, Michael Boll, 2003

机译：小鼠中肽转运蛋白Pept2基因的靶向破坏定义了其在肾脏中的生理作用

7. Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney [O] . Rubio-Aliaga, Isabel, Frey, Isabelle, Boll, Michael, 2003

机译：小鼠中肽转运蛋白Pept2基因的靶向破坏定义了其在肾脏中的生理作用

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4. TRANSGENIC MICE CONTAINING ABC TRANSPORTER-LIKE APTASE GENE DISRUPTIONS [P] . 外国专利： WO02079437A3 . 2003-04-03

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5. TRANSGENIC MICE CONTAINING ABC TRANSPORTER-LIKE APTASE GENE DISRUPTIONS [P] . 外国专利： WO02079437A2 . 2002-10-10

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Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney

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