| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INVITED REVIEW
Division of Genetic and Translational Medicine, Departments of Medicine, Pediatrics, and Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294
Numerous murine (mouse and rat) models of polycystic kidney disease (PKD) have been described in which the mutant phenotype results from a spontaneous mutation or engineering via chemical mutagenesis, transgenic technologies, or gene-specific targeting in mouse orthologs of human PKD genes. These murine phenotypes closely resemble human PKD, with common abnormalities observed in tubular epithelia, the interstitial compartment, and the extracellular matrix of cystic kidneys. In both human and murine PKD, genetic background appears to modulate the renal cystic phenotype. In murine models, these putative modifying effects have been dissected into discrete factors called quantitative trait loci and genetically mapped. Several lines of experimental evidence support the hypothesis that PKD genes and their modifiers may define pathways involved in cystogenesis and PKD progression. Among the various pathway abnormalities described in murine PKD, recent provocative data indicate that structural and/or functional defects in the primary apical cilia of tubular epithelia may play a key role in PKD pathogenesis. This review describes the most widely studied murine models; highlights the data regarding specific gene defects and genetic modifiers; summarizes the data from these models that have advanced our understanding of PKD pathogenesis; and examines the effect of various therapeutic interventions in murine PKD.
autosomal dominant polycystic kidney disease; autosomal recessive polycystic kidney disease; polycystic kidney disease quantitative trait loci; polycystic kidney disease therapeutics
This article has been cited by other articles:
|
|
 |
|
  F. Park, W. E. Sweeney, G. Jia, R. J. Roman, and E. D. Avner 20-HETE Mediates Proliferation of Renal Epithelial Cells in Polycystic Kidney Disease J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1929 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Sweeney Jr, R. O. von Vigier, P. Frost, and E. D. Avner Src Inhibition Ameliorates Polycystic Kidney Disease J. Am. Soc. Nephrol., July 1, 2008; 19(7): 1331 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Weber, E. K. Lee, U. Basavanna, S. Lindley, R. C. Ziegelstein, G. G. Germino, and M. Sutters Heterologous expression of polycystin-1 inhibits endoplasmic reticulum calcium leak in stably transfected MDCK cells Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1279 - F1286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Burtey, M. Riera, E. Ribe, P. Pennekamp, E. Passage, R. Rance, B. Dworniczak, and M. Fontes Overexpression of PKD2 in the mouse is associated with renal tubulopathy Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1157 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tao, I. Zafar, J. Kim, R. W. Schrier, and C. L. Edelstein Caspase-3 Gene Deletion Prolongs Survival in Polycystic Kidney Disease J. Am. Soc. Nephrol., April 1, 2008; 19(4): 749 - 755. [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Jauregui, K. C.Q. Nguyen, D. H. Hall, and M. M. Barr The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure J. Cell Biol., March 5, 2008; 180(5): 973 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Otto, M. L. Trapp, U. T. Schultheiss, J. Helou, L. M. Quarmby, and F. Hildebrandt NEK8 Mutations Affect Ciliary and Centrosomal Localization and May Cause Nephronophthisis J. Am. Soc. Nephrol., March 1, 2008; 19(3): 587 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Makita, Y. Uchijima, K. Nishiyama, T. Amano, Q. Chen, T. Takeuchi, A. Mitani, T. Nagase, Y. Yatomi, H. Aburatani, et al. Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ Am J Physiol Renal Physiol, March 1, 2008; 294(3): F542 - F553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Natoli, T. C. Gareski, W. R. Dackowski, L. Smith, N. O. Bukanov, R. J. Russo, H. Husson, D. Matthews, P. Piepenhagen, and O. Ibraghimov-Beskrovnaya Pkd1 and Nek8 mutations affect cell-cell adhesion and cilia in cysts formed in kidney organ cultures Am J Physiol Renal Physiol, January 1, 2008; 294(1): F73 - F83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tian, R. Kolb, J.-H. Hong, J. Carroll, D. Li, J. You, R. Bronson, M. B. Yaffe, J. Zhou, and T. Benjamin TAZ Promotes PC2 Degradation through a SCF{beta}-Trcp E3 Ligase Complex Mol. Cell. Biol., September 15, 2007; 27(18): 6383 - 6395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Garcia-Gonzalez, L. F. Menezes, K. B. Piontek, J. Kaimori, D. L. Huso, T. Watnick, L. F. Onuchic, L. M. Guay-Woodford, and G. G. Germino Genetic interaction studies link autosomal dominant and recessive polycystic kidney disease in a common pathway Hum. Mol. Genet., August 15, 2007; 16(16): 1940 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Condac, R. Silasi-Mansat, S. Kosanke, T. Schoeb, R. Towner, F. Lupu, R. D. Cummings, and M. E. Hinsdale Polycystic disease caused by deficiency in xylosyltransferase 2, an initiating enzyme of glycosaminoglycan biosynthesis PNAS, May 29, 2007; 104(22): 9416 - 9421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Olteanu, M. B. Hovater, and E. M. Schwiebert Intraluminal autocrine purinergic signaling within cysts: implications for the progression of diseases that involve encapsulated cyst formation Am J Physiol Renal Physiol, January 1, 2007; 292(1): F11 - F14. [Full Text] [PDF]
|
|
|
|
|
|
L. Battini, E. Fedorova, S. Macip, X. Li, P. D. Wilson, and G. L. Gusella Stable Knockdown of Polycystin-1 Confers Integrin-{alpha}2beta1-Mediated Anoikis Resistance J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3049 - 3058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Smith, N. O. Bukanov, H. Husson, R. J. Russo, T. C. Barry, A. L. Taylor, D. R. Beier, and O. Ibraghimov-Beskrovnaya Development of Polycystic Kidney Disease in Juvenile Cystic Kidney Mice: Insights into Pathogenesis, Ciliary Abnormalities, and Common Features with Human Disease J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2821 - 2831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Calvet MEK Inhibition Holds Promise for Polycystic Kidney Disease J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1498 - 1500. [Full Text] [PDF]
|
|
|
|
|
|
B. J. Siroky, W. B. Ferguson, A. L. Fuson, Y. Xie, A. Fintha, P. Komlosi, B. K. Yoder, E. M. Schwiebert, L. M. Guay-Woodford, and P. D. Bell Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1320 - F1328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Gray Primary cilia and regulation of renal Na+ transport. Focus on "Heightened epithelial Na+ channel-mediated Na+ absorption in a murine polycystic kidney disease model epithelium lacking apical monocilia" Am J Physiol Cell Physiol, April 1, 2006; 290(4): C947 - C949. [Full Text] [PDF]
|
|
|
|
|
|
D. Olteanu, B. K. Yoder, W. Liu, M. J. Croyle, E. A. Welty, K. Rosborough, J. M. Wyss, P. D. Bell, L. M. Guay-Woodford, M. O. Bevensee, et al. Heightened epithelial Na+ channel-mediated Na+ absorption in a murine polycystic kidney disease model epithelium lacking apical monocilia Am J Physiol Cell Physiol, April 1, 2006; 290(4): C952 - C963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Allen, K. B. Piontek, E. Garrett-Mayer, M. Garcia-Gonzalez, K. L. Gorelick, and G. G. Germino Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors Hum. Mol. Genet., January 1, 2006; 15(1): 11 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Banizs, M. M. Pike, C. L. Millican, W. B. Ferguson, P. Komlosi, J. Sheetz, P. D. Bell, E. M. Schwiebert, and B. K. Yoder Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus Development, December 1, 2005; 132(23): 5329 - 5339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Davenport and B. K. Yoder An incredible decade for the primary cilium: a look at a once-forgotten organelle Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1159 - F1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Brown, M.-T. Bihoreau, S. Hoffmann, B. Kranzlin, I. Tychinskaya, N. Obermuller, D. Podlich, S. N. Boehn, P. J. Kaisaki, N. Megel, et al. Missense Mutation in Sterile {alpha} Motif of Novel Protein SamCystin is Associated with Polycystic Kidney Disease in (cy/+) Rat J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3517 - 3526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Mahjoub, M. L. Trapp, and L. M. Quarmby NIMA-Related Kinases Defective in Murine Models of Polycystic Kidney Diseases Localize to Primary Cilia and Centrosomes J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3485 - 3489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Sharp, L M Messiaen, G Page, C Antignac, M-C Gubler, L F Onuchic, S Somlo, G G Germino, and L M Guay-Woodford Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts J. Med. Genet., April 1, 2005; 42(4): 336 - 349. [Full Text] [PDF]
|
|
|
|
|
|
W. M. Bennett V2 Receptor Antagonists in Cystic Kidney Diseases: An Exciting Step towards a Practical Treatment J. Am. Soc. Nephrol., April 1, 2005; 16(4): 838 - 839. [Full Text] [PDF]
|
|
|
|
|
|
M. Mrug, R. Li, X. Cui, T. R. Schoeb, G. A. Churchill, and L. M. Guay-Woodford Kinesin Family Member 12 Is a Candidate Polycystic Kidney Disease Modifier in the cpk Mouse J. Am. Soc. Nephrol., April 1, 2005; 16(4): 905 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Veizis and C. U. Cotton Abnormal EGF-dependent regulation of sodium absorption in ARPKD collecting duct cells Am J Physiol Renal Physiol, March 1, 2005; 288(3): F474 - F482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tong and J. D. Stockand Receptor tyrosine kinases mediate epithelial Na+ channel inhibition by epidermal growth factor Am J Physiol Renal Physiol, January 1, 2005; 288(1): F150 - F161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. L.-v. Leeuwen, J. G. Dauwerse, H. J. Baelde, W. N. Leonhard, A. van de Wal, C. J. Ward, S. Verbeek, M. C. DeRuiter, M. H. Breuning, E. de Heer, et al. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease Hum. Mol. Genet., December 15, 2004; 13(24): 3069 - 3077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhang, P. D. Taulman, and B. K. Yoder Cystic Kidney Diseases: All Roads Lead to the Cilium Physiology, August 1, 2004; 19(4): 225 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nurnberger, A. Kribben, A. O. Saez, G. Heusch, T. Philipp, and C. L. Phillips The Invs Gene Encodes a Microtubule-Associated Protein J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1700 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Phillips, K. J. Miller, A. J. Filson, J. Nurnberger, J. L. Clendenon, G. W. Cook, K. W. Dunn, P. A. Overbeek, V. H. Gattone II, and R. L. Bacallao Renal Cysts of inv/inv Mice Resemble Early Infantile Nephronophthisis J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1744 - 1755. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
