Pattern of Expression of γ-Glutamyl Transpeptidase in Rat Liver and Kidney During Development

Jacquemin, Emmanuel; Bulle, Frédérique; Bernaudin, Jean-François; Wellman, Maria; Hugon, R. N.; Guellaën, Georges; Hadchouel, Michelle

doi:10.1097/00005176-199007000-00018

Cited by 21 publications

(15 citation statements)

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“…Significant expression of γGT (encoded by Ggt1) occurs in the renal proximal tubule beginning 2-3 weeks after birth, when nephrogenesis is virtually complete (29). The Ggt1 promoter has been used to successfully target different genes of interest specifically to the renal proximal tubule (28).…”

Section: Resultsmentioning

confidence: 99%

“…Homozygous deletion of Pten is embryonically lethal before midgestation (26). Therefore, we used a Cre/LoxP strategy to delete Pten specifically in renal proximal tubules (Ggt1-Cre Pten fl/fl , herein referred to as Pten ptKO ) (27,28), making use of the promoter Ggt1, which is not active in that nephron segment until nephrogenesis is virtually complete (28,29).…”

Section: Phosphatidylinositol 3-kinase Signaling Determines Kidney Sizementioning

confidence: 99%

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Phosphatidylinositol 3-kinase signaling determines kidney size

Chen¹,

Nagai²,

Chen³

et al. 2015

J. Clin. Invest.

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Section: Resultsmentioning

confidence: 99%

Section: Phosphatidylinositol 3-kinase Signaling Determines Kidney Sizementioning

confidence: 99%

Phosphatidylinositol 3-kinase signaling determines kidney size

Chen¹,

Nagai²,

Chen³

et al. 2015

J. Clin. Invest.

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“…[41][42][43][44] Mice with the tamoxifen-inducible Cited1-Cre recombinase (Cited1-CreER T2 ) were developed as previously described. 45 Mice with a conditional activating mutation of CNNTB1 in which exon 3 is flanked by lox sites (Catnb lox[ex3] ) were a gift from Dr. Makoto M. Taketo (Kyoto University, Kyoto, Japan).…”

Section: Micementioning

confidence: 99%

“…To define whether activating mutations of ␤-catenin caused tumors only in the developing mesenchyme or whether this was a more generalized occurrence in the tumor, an activating mutation of ␤-catenin was knocked into the proximal tubular epithelium using a ␥GT renal-specific cre recombinase to give rise to mice with the genotype ␥GT-Cre/Catnb ϩ/lox(ex3) (GCatnb ⌬ex3 ). [41][42][43][44] ␥GT expression in the kidney is restricted to the proximal tubule and begins approximately on postnatal day 10, which is toward the end of nephron development. 41,44 The G-Catnb ⌬ex3 mice were born at the expected frequency but had a minimal, but significant, decrement in survival compared with control animals (P ϭ 0.04) ( Figure 1E).…”

Section: Deleting Exon 3 Of Cnntb1 In the Proximal Tubule Induces Primentioning

confidence: 99%

“…[41][42][43][44] ␥GT expression in the kidney is restricted to the proximal tubule and begins approximately on postnatal day 10, which is toward the end of nephron development. 41,44 The G-Catnb ⌬ex3 mice were born at the expected frequency but had a minimal, but significant, decrement in survival compared with control animals (P ϭ 0.04) ( Figure 1E). In mice younger than 25 weeks (n ϭ 7), there were no discernable gross or histologic abnormalities of the kidneys (data not shown).…”

Section: Deleting Exon 3 Of Cnntb1 In the Proximal Tubule Induces Primentioning

confidence: 99%

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β-Catenin and K-RAS Synergize to Form Primitive Renal Epithelial Tumors with Features of Epithelial Wilms' Tumors

Clark

Polosukhina

Love

et al. 2011

The American Journal of Pathology

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Wilms' tumor (WT) is the most common childhood renal cancer. Although mutations in known tumorassociated genes (WT1, WTX , and CATNB) occur only in a third of tumors, many tumors show evidence of activated ␤-catenin-dependent Wnt signaling, but the molecular mechanism by which this occurs is unknown. A key obstacle to understanding the pathogenesis of WT is the paucity of mouse models that recapitulate its features in humans. Herein, we describe a transgenic mouse model of primitive renal epithelial neoplasms that have high penetrance and mimic the epithelial component of human WT. Introduction of a stabilizing ␤-catenin mutation restricted to the kidney is sufficient to induce primitive renal epithelial tumors; however, when compounded with activation of K-RAS, the mice develop large, bilateral, Wilms' tumor (WT) is an embryonal tumor of the kidney that is the most common childhood renal cancer and the fourth most common childhood malignancy overall. 1,2Modern multimodal management can cure 95% of patients with WT with the most favorable risk profile 3-7 but at the cost of significant short-and long-term morbidity. -11In addition, there remains a persistent cohort of children who ultimately fail therapy and die.3 Consequently, the main research priorities for WT are to lower the toxicity while maintaining efficacy of existing therapy for lowerrisk patients and to develop novel therapeutics for higherrisk patients. Achieving these goals depends on understanding the mechanisms underlying WT oncogenesis and progression.WTs are triphasic, embryonic tumors that classically have varying amounts of blastemal elements, primitive mesenchymal stroma, and primitive epithelia. They are generally thought to arise from nephrogenic rests (ie, embryonic tissue) derived from the metanephric mesenchyme during renal development. The genetic aberrations underlying this process are known to be heterogeneous 12 and can include inactivating mutations of Wilms' tumor 1 gene (WT1), 13,14 Wilms' tumor gene found on chromosome X (WTX), [15][16][17] and stabilizing/activating mutations of ␤-catenin (CTNNB1). 18,19 The precise mechaSupported in part by NIH grants K08 CA113452 (P.E.C.), DK065123 (R.Z.), DK075594 (R.Z.), DK65123 (R.Z.), and P30 DK079341 (P.E.C. and R.Z.); an American Heart Association Established Investigator Award (R.Z.); and a Merit Award from the Department of Veterans Affairs (R.Z.).Accepted for publication August 10, 2011. CME Disclosure: None of the authors disclosed any relevant financial relationships.Address reprint requests to Peter E. Clark, M.D., Associate Professor Urologic Surgery, Vanderbilt University Medical Center, A-1302 Medical Center North, Nashville, TN 37232-2765. E-mail: peter.clark@ vanderbilt.edu.

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Characterization of transcriptional regulation of γ-glutamyl transpeptidase in rat liver involving both positive and negative regulatory elements

1997

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gamma-Glutamyl transpeptidase is normally not present in adult rat hepatocytes, but its expression is induced by a range of xenobiotics, including carcinogens and chemopreventive agents. Synthesis of the enzyme is mediated by at least six mRNAs transcribed from tandemly arranged promoters on a single gene. We previously identified and partially characterized promoter III as being responsible for upregulation of gamma-glutamyl transpeptidase in rat liver in response to inducing agents. In this study, we examined response elements involved in the regulation of this promoter by using reporter gene assays and in vitro DNase I footprinting and electrophoretic mobility shift assays. Among the response elements was a region with negative regulatory activity upstream of a 240-bp basal regulatory region covering the transcriptional start site. This negative regulatory region, lying between nt -465 and -185, contained sequences with considerable homology to silencer elements in the glutathione s-transferase P gene. The region of basal regulation (nt -185 to +55) contained a CCAAT box, a TFIID binding site, and a GAGA box. A hepatocyte nuclear factor 3-like sequence was identified at nt -234 to -254 and had a DNase I hypersensitive site characteristic of binding of members of the hepatocyte nuclear factor 3/fork head family of proteins and may be involved in the regulation of this promoter.

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Pattern of Expression of γ-Glutamyl Transpeptidase in Rat Liver and Kidney During Development

Cited by 21 publications

References 0 publications

Phosphatidylinositol 3-kinase signaling determines kidney size

Phosphatidylinositol 3-kinase signaling determines kidney size

β-Catenin and K-RAS Synergize to Form Primitive Renal Epithelial Tumors with Features of Epithelial Wilms' Tumors

Characterization of transcriptional regulation of γ-glutamyl transpeptidase in rat liver involving both positive and negative regulatory elements

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