Murine Congenital Polycystic Kidney Disease: A Model for Studying Development of Cystic Disease

Preminger, Glenn M.; Koch, William E.; Fried, Floyd A.; McFarland, Eleanor C.; Murphy, Edwin D.; Mandell, James

doi:10.1016/s0022-5347(17)53911-7

Cited by 94 publications

(44 citation statements)

References 11 publications

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“…The Cys1 cpk mouse is an ARPKD phenocopy that closely resembles the human disease course with its renal and extrarenal manifestations, 57,58 unlike orthologous mouse ARPKD models that lack the typical ARPKD-like renal cystic phenotype. The Cys1 cpk mutation, which arose spontaneously in the C57BL/6J-Pldn pa strain, involves a tandem deletion that leads to the truncation of a novel, cilia-associated protein called cystin.…”

Section: Cys1mentioning

confidence: 99%

Kidney Injury Accelerates Cystogenesis via Pathways Modulated by Heme Oxygenase and Complement

Zhou¹,

Ouyang²,

Schoeb³

et al. 2012

Journal of the American Society of Nephrology

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AKI accelerates cystogenesis. Because cystogenic mutations induce strong transcriptional responses similar to those seen after AKI, these responses may accelerate the progression of cystic renal disease. Here, we modulated the severity of the AKI-like response in Cys1 cpk/cpk mice, a model that mimics autosomal recessive polycystic kidney disease. Specifically, we induced or inhibited activity of the renoprotective enzyme heme oxygenase (HO) and determined the effects on renal cystogenesis. We found that induction of HO attenuated both renal injury and the rate of cystogenesis, whereas inhibition of HO promoted cystogenesis. HO activity mediated the response of NFkB, which is a hallmark transcriptional feature common to both cystogenesis and AKI. Among the HO-modulated effects we measured, expression of complement component 3 (C3) strongly correlated with cystogenesis, a functionally relevant association as suggested by Cys1 cpk/cpk mice with genetically induced C3 deficiency. Because both C3 deficiency and HO induction reduce cyst number and cyst areas, these two factors define an injury-stimulated cystogenic pathway that may provide therapeutic targets to slow the formation of new renal cysts and the growth of existing cysts.

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Section: Cys1mentioning

confidence: 99%

Kidney Injury Accelerates Cystogenesis via Pathways Modulated by Heme Oxygenase and Complement

Zhou¹,

Ouyang²,

Schoeb³

et al. 2012

Journal of the American Society of Nephrology

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“…[3][4][5][6][7] These models have proven very useful in elucidating the roles of altered cell proliferation, cell differentiation, extracellular matrix composition, ionic transport, and oncogene expression in the development of PKD. The best characterized models are the congenital PKD mouse (cpk) 3 and the Oak Ridge PKD mouse (Tg737/orpk). 4 Although murine models of PKD share many features in common in the kidney, there is some variation in extrarenal cystic disease.…”

mentioning

confidence: 99%

ADP-Ribosylation Factor-Like 3 Is Involved in Kidney and Photoreceptor Development

Schrick

Vogel

Abuin

et al. 2006

The American Journal of Pathology

140

114

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ADP-ribosylation factor-like 3 (Arl3) is a member of a small subfamily of G-proteins involved in membraneassociated vesicular and intracellular trafficking processes. Genetic studies in Leishmania have shown that the Arl3 homolog is essential for flagellum biogenesis. Mutations in a related human family member, Arl6, result in Bardet-Biedl syndrome in humans, which is characterized by genital, renal, and retinal abnormalities, obesity, and learning deficits. As part of our largescale phenotypic screen, mice deficient for the Arl3 gene were generated and analyzed. Arl3 (؊/؊) mice were born at a sub-Mendelian ratio, were small and sickly, and had markedly swollen abdomens. These mutants failed to thrive, and all died by 3 weeks of age. The (؊/؊) mice exhibited abnormal development of renal, hepatic, and pancreatic epithelial tubule structures, which is characteristic of the renal-hepatic-pancreatic dysplasia found in autosomal recessive polycystic kidney disease. Absence of Arl3 was associated with abnormal epithelial cell proliferation and cyst formation. Moreover, mice lacking Arl3 exhibited photoreceptor degeneration as early as postnatal day 14. These results are the first to implicate Arl3 in a ciliary disease affecting the kidney, biliary tract, pancreas, and retina.

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“…The adult type is an autosomal dominant polycystic kidney disease (ADPKD) and the infant type is an autosomal recessive polycystic kidney disease (ARPKD). Although many spontaneously occurring polycystic kidney mouse models have been established [1,3,4,8,10,12,13], the Cy rat [2,5,6,11] and the chin rat [9] are the only rat models. At Charles River Japan Inc., we have identified a female rat with polycysts on both the kidney and liver derived from an ongoing colony of Crj:CD (SD) rats.…”

mentioning

confidence: 99%

Characterization of a Novel Polycystic Kidney Rat Model with Accompanying Polycystic Liver.

Katsuyama¹,

Masuyama

Kōmura³

et al. 2000

Exp. Anim.

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Abstract:A polycystic kidney rat model is being established from a Crj:CD (SD) rat strain. Unlike existing animal models of polycystic kidney disease, this mutant rat has a completely polycystic liver. Mating experiments revealed that the phenotype is controlled by an autosomal recessive gene. We propose that this gene be tentatively called the "rpc" gene. Key words: polycystic kidney, polycystic liver, rat Polycystic kidney disease (PKD) is a hereditary disorder that comes in two forms, adult polycystic kidney disease (APKD), and infantile polycystic kidney disease (IPKD). The adult type is an autosomal dominant polycystic kidney disease (ADPKD) and the infant type is an autosomal recessive polycystic kidney disease (ARPKD). Although many spontaneously occurring polycystic kidney mouse models have been established [1,3,4,8,10,12,13], the Cy rat [2,5,6,11] and the chin rat [9] are the only rat models. At Charles River Japan Inc., we have identified a female rat with polycysts on both the kidney and liver derived from an ongoing colony of Crj:CD (SD) rats. Development of a PKD model animal (hereinafter referred to as the PCK rat) with polycysts on both the kidney and liver was initiated by sib mating offspring of the female animal. Continuous sib mating since 1996 has led to the establishment of a rat model for PKD via an inbred strain originating from the Crj:CD (SD) rat, which is now in its twelfth generation. During this period, characteriza- (Received 27 April 1999 / Accepted 14 September 1999)Address corresponding: M. Katsuyama, Charles River Japan Inc., 10210-6, Tana, Sagamihara, Kanagawa 229-1124, Japan tion of the PCK rat and mating experiments with other strains were also performed, the results of which are reported here.The animal rooms were maintained at a temperature of 19-25°C, humidity of 40-80% with a 12 hr lightdark cycle (06:00-18:00). The animals were given ad libitum access to commercial feed CRF-1 (Oriental yeast Co., Ltd.) and tap-water. Body weight was measured every week from 3 to 111 weeks of age, and survival rate was documented during a general examination of the condition of the animals. The bilateral kidneys and liver were weighed at 5, 15, 25 and 35 weeks of age, and compared with that of the original Crj:CD (SD) rat strain. For histopathological examination, kidney and liver were fixed with 10% formalin, and according to standard procedures, were then paraffin sliced, HE stained, and examined by microscopy. In order to analyze the mode of inheritance, F3-F5 generation pck rats were mated with Crj:CD (SD) rats, bred in a room separate to that of PCK rats, and F344/DuCrj rats. Off-

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Murine Congenital Polycystic Kidney Disease: A Model for Studying Development of Cystic Disease

Cited by 94 publications

References 11 publications

Kidney Injury Accelerates Cystogenesis via Pathways Modulated by Heme Oxygenase and Complement

Kidney Injury Accelerates Cystogenesis via Pathways Modulated by Heme Oxygenase and Complement

ADP-Ribosylation Factor-Like 3 Is Involved in Kidney and Photoreceptor Development

Characterization of a Novel Polycystic Kidney Rat Model with Accompanying Polycystic Liver.

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