Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 14

Publication Record

Connections

Inactivation of in Abcg2 lineage-derived cells drives the appearance of polycystic lesions and fibrosis in the adult kidney.
Gewin LS, Summers ME, Harral JW, Gaskill CF, Khodo SN, Neelisetty S, Sullivan TM, Hopp K, Reese JJ, Klemm DJ, Kon V, Ess KC, Shi W, Majka SM
(2019) Am J Physiol Renal Physiol 317: F1201-F1210
MeSH Terms: ATP Binding Cassette Transporter, Subfamily G, Member 2, Animals, Cell Lineage, Female, Fibrosis, Kidney Tubules, Proximal, Male, Mice, Myofibroblasts, Polycystic Kidney Diseases, Selective Estrogen Receptor Modulators, Tamoxifen, Tuberous Sclerosis Complex 2 Protein
Show Abstract · Added March 18, 2020
Tuberous sclerosis complex 2 (TSC2), or tuberin, is a pivotal regulator of the mechanistic target of rapamycin signaling pathway that controls cell survival, proliferation, growth, and migration. Loss of function manifests in organ-specific consequences, the mechanisms of which remain incompletely understood. Recent single cell analysis of the kidney has identified ATP-binding cassette G2 (Abcg2) expression in renal proximal tubules of adult mice as well as a in a novel cell population. The impact in adult kidney of knockdown in the Abcg2-expressing lineage has not been evaluated. We engineered an inducible system in which expression of truncated , lacking exons 36-37 with an intact 3' region and polycystin 1, is driven by Here, we demonstrate that selective expression of in the Abcg2 lineage drives recombination in proximal tubule epithelial and rare perivascular mesenchymal cells, which results in progressive proximal tubule injury, impaired kidney function, formation of cystic lesions, and fibrosis in adult mice. These data illustrate the critical importance of function in the Abcg2-expressing proximal tubule epithelium and mesenchyme during the development of cystic lesions and remodeling of kidney parenchyma.
0 Communities
2 Members
0 Resources
13 MeSH Terms
Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice.
Zeng F, Miyazawa T, Kloepfer LA, Harris RC
(2014) Kidney Int 86: 538-47
MeSH Terms: Animals, Apoptosis, Blood Urea Nitrogen, Caspase 3, Cell Proliferation, Cyclin D, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Disease Models, Animal, Disease Progression, Epithelial Cells, Fibrosis, Gene Deletion, Kidney Cortex, Kidney Medulla, Mice, Organ Size, Polycystic Kidney Diseases, Receptor, ErbB-4
Show Abstract · Added October 27, 2014
ErbB4 is highly expressed in the cystic kidneys with polycystic kidney diseases. To investigate its potential role in cystogenesis, cpk mice carrying a heart-rescued ErbB4 deletion were generated. Accelerated cyst progression and renal function deterioration were noted as early as 10 days postnatally in cpk mice with ErbB4 deletion compared to cpk mice, as indicated by increased cystic index, higher kidney weight to body weight ratios, and elevated BUN levels. No apparent defects in renal development were noted with ErbB4 deletion itself. Increased cell proliferation was predominately seen in the cortex of cystic kidneys with or without ErbB4 deletion. However, there was significantly more cell proliferation in the cyst-lining epithelial cells in cpk mice with ErbB4 deletion. TUNEL staining localized apoptotic cells mainly to the renal medulla. There were significantly more apoptotic cells in the cyst-lining epithelial cells in ErbB4-deleted cpk kidneys, with decreased levels of cyclin D1, increased levels of p21, p27, and cleaved caspase 3. Thus, lack of ErbB4 may contribute to elevated cell proliferation and unbalanced cell apoptosis, resulting in accelerated cyst formation and early renal function deterioration. These studies suggest that the high level of ErbB4 expression seen in cpk mice may exert relative cytoprotective effects in renal epithelia.
1 Communities
1 Members
0 Resources
19 MeSH Terms
Acute decompensation of allograft function in a kidney transplant recipient.
Christopher D, McElmurray JH, Shaffer D, Schaefer HM
(2013) Am J Transplant 13: 3284-5; quiz 3286
MeSH Terms: Angiography, Blood Pressure, Brain Abscess, Graft Survival, Humans, Hypertension, Kidney, Kidney Transplantation, Male, Middle Aged, Polycystic Kidney Diseases, Renal Insufficiency, Seizures
Added February 25, 2014
0 Communities
1 Members
0 Resources
13 MeSH Terms
An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice.
Traykova-Brauch M, Schönig K, Greiner O, Miloud T, Jauch A, Bode M, Felsher DW, Glick AB, Kwiatkowski DJ, Bujard H, Horst J, von Knebel Doeberitz M, Niggli FK, Kriz W, Gröne HJ, Koesters R
(2008) Nat Med 14: 979-84
MeSH Terms: Animals, Disease Models, Animal, Doxycycline, Fibrosis, Immunohistochemistry, Kidney Tubules, Mice, Mice, Transgenic, PAX8 Transcription Factor, Paired Box Transcription Factors, Polycystic Kidney Diseases, Promoter Regions, Genetic, Trans-Activators, Transforming Growth Factor beta1, Tuberous Sclerosis Complex 1 Protein, Tumor Suppressor Proteins
Show Abstract · Added September 9, 2013
We describe a transgenic mouse line, Pax8-rtTA, which, under control of the mouse Pax8 promoter, directs high levels of expression of the reverse tetracycline-dependent transactivator (rtTA) to all proximal and distal tubules and the entire collecting duct system of both embryonic and adult kidneys. Using crosses of Pax8-rtTA mice with tetracycline-responsive c-MYC mice, we established a new, inducible model of polycystic kidney disease that can mimic adult onset and that shows progression to renal malignant disease. When targeting the expression of transforming growth factor beta-1 to the kidney, we avoided early lethality by discontinuous treatment and successfully established an inducible model of renal fibrosis. Finally, a conditional knockout of the gene encoding tuberous sclerosis complex-1 was achieved, which resulted in the early outgrowth of giant polycystic kidneys reminiscent of autosomal recessive polycystic kidney disease. These experiments establish Pax8-rtTA mice as a powerful tool for modeling renal diseases in transgenic mice.
0 Communities
0 Members
1 Resources
16 MeSH Terms
The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.
Lehman JM, Michaud EJ, Schoeb TR, Aydin-Son Y, Miller M, Yoder BK
(2008) Dev Dyn 237: 1960-71
MeSH Terms: Animals, Cilia, Disease Models, Animal, Epithelial Cells, Humans, Mice, Mice, Transgenic, Polycystic Kidney Diseases, Tumor Suppressor Proteins
Show Abstract · Added March 31, 2020
The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can be analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.
Copyright (c) 2008 Wiley-Liss, Inc.
0 Communities
1 Members
0 Resources
MeSH Terms
Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice.
Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ
(2007) Hum Mol Genet 16: 3188-96
MeSH Terms: Age of Onset, Animals, Animals, Newborn, Animals, Suckling, Cell Proliferation, Cysts, Gene Deletion, Gene Expression Regulation, Germ-Line Mutation, Kidney, Lactation, Mice, Mice, Transgenic, Models, Biological, Organ Specificity, Polycystic Kidney Diseases, TRPP Cation Channels, Tamoxifen, Time Factors
Show Abstract · Added September 9, 2013
Autosomal dominant polycystic kidney disease, caused by mutations in the PKD1 gene, is characterized by progressive deterioration of kidney function due to the formation of thousands of cysts leading to kidney failure in mid-life or later. How cysts develop and grow is currently unknown, although extensive research revealed a plethora of cellular changes in cyst lining cells. We have constructed a tamoxifen-inducible, kidney epithelium-specific Pkd1-deletion mouse model. Upon administration of tamoxifen to these mice, a genomic fragment containing exons 2-11 of the Pkd1-gene is specifically deleted in the kidneys and cysts are formed. Interestingly, the timing of Pkd1-deletion has strong effects on the phenotype. At 1 month upon gene disruption, adult mice develop only a very mild cystic phenotype showing some small cysts and dilated tubules. Young mice, however, show massive cyst formation. In these mice, at the moment of gene disruption, cell proliferation takes place to elongate the nephron. Our data indicate that Pkd1 gene deficiency does not initiate sufficient autonomous cell proliferation leading to cyst formation and that additional stimuli are required. Furthermore, we show that one germ-line mutation of Pkd1 is already associated with increased proliferation.
0 Communities
0 Members
1 Resources
19 MeSH Terms
Membranoproliferative injury pattern in a renal allograft.
Gökden N, Rossini M, Kumar J, Fogo AB
(2005) Am J Kidney Dis 46: 573-6
MeSH Terms: Acute Disease, Cadaver, Capillaries, Complement C4b, Diabetes Mellitus, Type 2, Female, Glomerulonephritis, Membranoproliferative, Graft Rejection, Humans, Hypertension, Immunosuppressive Agents, Kidney Glomerulus, Kidney Transplantation, Microscopy, Electron, Microscopy, Fluorescence, Middle Aged, Peptide Fragments, Polycystic Kidney Diseases, Postoperative Complications, Transplantation, Homologous
Added January 20, 2012
1 Communities
1 Members
0 Resources
20 MeSH Terms
PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells.
Zhang MZ, Mai W, Li C, Cho SY, Hao C, Moeckel G, Zhao R, Kim I, Wang J, Xiong H, Wang H, Sato Y, Wu Y, Nakanuma Y, Lilova M, Pei Y, Harris RC, Li S, Coffey RJ, Sun L, Wu D, Chen XZ, Breyer MD, Zhao ZJ, McKanna JA, Wu G
(2004) Proc Natl Acad Sci U S A 101: 2311-6
MeSH Terms: Adult, Animals, Base Sequence, Cell Line, Cell Line, Tumor, Cloning, Molecular, DNA Primers, Fetus, Humans, Immunohistochemistry, Kidney, Mice, Polycystic Kidney Diseases, Receptors, Cell Surface, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic
Show Abstract · Added December 10, 2013
Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been shown to cause autosomal recessive polycystic kidney disease (ARPKD), but the cellular functions of the gene product (PKHD1) remain uncharacterized. To illuminate its properties, the spatial and temporal expression patterns of PKHD1 were determined in mouse, rat, and human tissues by using polyclonal Abs and mAbs recognizing various specific regions of the gene product. During embryogenesis, PKHD1 is widely expressed in epithelial derivatives, including neural tubules, gut, pulmonary bronchi, and hepatic cells. In the kidneys of the pck rats, the rat model of which is genetically homologous to human ARPKD, the level of PKHD1 was significantly reduced but not completely absent. In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia. Immunoreactive PKHD1 localized predominantly at the apical domain of polarized epithelial cells, suggesting it may be involved in the tubulogenesis and/or maintenance of duct-lumen architecture. Reduced PKHD1 levels in pck rat kidneys and its colocalization with polycystins may underlie the pathogenic basis for cystogenesis in polycystic kidney diseases.
2 Communities
3 Members
0 Resources
17 MeSH Terms
Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease.
Lin F, Hiesberger T, Cordes K, Sinclair AM, Goldstein LS, Somlo S, Igarashi P
(2003) Proc Natl Acad Sci U S A 100: 5286-91
MeSH Terms: Animals, Base Sequence, Blotting, Northern, Calcium-Binding Proteins, Cilia, DNA Primers, In Situ Nick-End Labeling, Kidney, Kinesin, Mice, Mice, Knockout, Mice, Transgenic, Microscopy, Electron, Scanning, Muscle Proteins, Polycystic Kidney Diseases, Reverse Transcriptase Polymerase Chain Reaction
Show Abstract · Added September 9, 2013
Polycystic kidney disease (PKD) is the most common genetic cause of renal failure in humans. Several proteins that are encoded by genes associated with PKD have recently been identified in primary cilia in renal tubular epithelia. These findings have suggested that abnormalities in cilia formation and function may play a role in the pathogenesis of PKD. To directly determine whether cilia are essential to maintain tubular integrity, we conditionally inactivated KIF3A, a subunit of kinesin-II that is essential for cilia formation, in renal epithelia. Constitutive inactivation of KIF3A produces abnormalities of left-right axis determination and embryonic lethality. Here we show that tissue-specific inactivation of KIF3A in renal tubular epithelial cells results in viable offspring with normal-appearing kidneys at birth. Cysts begin to develop in the kidney at postnatal day 5 and cause renal failure by postnatal day 21. The cyst epithelial cells lack primary cilia and exhibit increased proliferation and apoptosis, apical mislocalization of the epidermal growth factor receptor, increased expression of beta-catenin and c-Myc, and inhibition of p21(CIP1). These results demonstrate that the absence of renal cilia produces both the clinical and cell biological findings associated with PKD. Most generally, the phenotype of Kif3a mutant mice suggests a role for primary cilia in the maintenance of lumen-forming epithelial differentiation.
0 Communities
0 Members
1 Resources
16 MeSH Terms
Tubular basement membrane changes in 2-amino-4,5-diphenylthiazole-induced polycystic disease.
Butkowski RJ, Carone FA, Grantham JJ, Hudson BG
(1985) Kidney Int 28: 744-51
MeSH Terms: Amino Acids, Animals, Basement Membrane, Electrophoresis, Polyacrylamide Gel, Kidney Glomerulus, Kidney Tubules, Male, Molecular Weight, Peptides, Polycystic Kidney Diseases, Rats, Rats, Inbred Strains, Thiazoles
Show Abstract · Added December 10, 2013
Polycystic renal disease was induced in rats by feeding 2-amino-4,5-diphenylthiazole. Tubular (TBM) and glomerular basement membranes (GBM) were purified and analyzed for possible structural changes that may be a factor in the development of the tubular dilations and cysts. Changes in the relative quantities of TBM polypeptides were detected by sodium dodecylsulfate polyacrylamide gel electrophoresis. An overall increase in the concentration of high molecular weight components and a decrease in concentration of those of low molecular weight components were observed. Changes which were particularly notable included a twofold increase in a component of Mr = 380,000 and a decrease in one of Mr = 55,000 as analyzed without reduction of disulfide bonds. With reduction of disulfide bonds, the Mr = 380,000 component dissociates, whereas the Mr = 55,000 polypeptide does not, and polypeptides of Mr = 245,000 and 145,000 are observed to does not, and polypeptides of Mr = 245,000 and 145,000 are observed to increase about twofold in concentration (approximate molecular weights were determined using globular protein standards). These changes take place most rapidly from 4 to 8 weeks of drug administration and remain relatively constant between 8 and 16 weeks. If feeding of the drug is discontinued, the distribution of TBM polypeptides returns to normal. These results indicate that tubular basement membrane from animals with 2-amino-4,5-diphenylthiazole-induced polycystic renal disease is abnormal, and this should be considered as a possible contributing factor in the formation of cysts.
1 Communities
1 Members
0 Resources
13 MeSH Terms