A Mutant Rat with Congenital Skeletal Abnormalities and Polycystic Kidneys

Ohno, Kyoko; Kondo, Kiyoshi

doi:10.1538/expanim1978.38.2_139

Cited by 10 publications

(9 citation statements)

References 7 publications

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“…The strain of these rats with polycystic kidney has been maintained up to the present. However, the report by Ohno et al [6] did not evaluate the renal tissue of these rats in detail. Therefore, we observed their renal tissue by light microscopy, im munohistochemical methods, and electron microscopy.…”

Section: Discussionmentioning

confidence: 93%

“…We histologically evaluated rat ARPK reported by Ohno et al [6] who detected mutants showing skeletal abnormalities and polycystic kidneys among Wistar rats, and demonstrated by evaluation of the family history and a mating experiment that these abnormalities are con trolled by a single recessive gene. The strain of these rats with polycystic kidney has been maintained up to the present.…”

Section: Discussionmentioning

confidence: 99%

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Autosomal Recessive Polycystic Kidney in Rats

Inage

Kikkawa

Minato

et al. 1991

Nephron

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We evaluated the characteristics of renal lesions in rat autosomal recessive polycystic kidney (ARPK). In rat ARPK, small cysts appeared primarily in the medulla 2 months after birth and gradually extended to the cortex, forming large cysts involving the entire layer after 8 months. By immunofluorescence microscopy, type IV collagen was more strongly stained in the epithelial basement membrane of the rat ARPK than in the normal rat tubular basement membrane (TBM). Electron microscopy demonstrated a marked thickening, slight splitting and lamination of the TBM in the ARPK. As peroxidase-labeled lectins, dolichos biflorus very strongly stained the cyst epithelium whereas lens culinaris did not. These findings indicate that cysts in rat ARPK originate in the collecting duct.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Autosomal Recessive Polycystic Kidney in Rats

Inage

Kikkawa

Minato

et al. 1991

Nephron

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“…The Wistar-chi or rat ARPK model was described more than 10 years ago (59,104). In this autosomal recessive trait, the phenotype is characterized by growth retardation, polycystic kidneys, and abnormalities of the cranium, limbs, and axial skeleton.…”

Section: Rat Pkd Modelsmentioning

confidence: 99%

Murine models of polycystic kidney disease: molecular and therapeutic insights

Guay‐Woodford

2003

American Journal of Physiology-Renal Physiology

176

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Guay-Woodford, Lisa M. Murine models of polycystic kidney disease: molecular and therapeutic insights. Am J Physiol Renal Physiol 285: F1034-F1049, 2003 10.1152/ajprenal. 00195.2003.-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 RENAL TUBULAR CYSTS DEVELOP in several inherited human disorders. Among these, the polycystic kidney diseases (PKD) are one of the leading causes of endstage renal disease in children and adults (31). Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1:1,000 individuals, primarily as the result of mutations in one of two genes, PKD1 or PKD2 (81,(150)(151)(152). In comparison, autosomal recessive polycystic kidney disease (ARPKD) is much less frequent (1: 20,000 live births) and results primarily from mutations in a single gene, PKHD1 (107, 162).The principal pathological manifestations in PKD involve 1) the formation of epithelial-lined cysts throughout the nephron in ADPKD and predominantly in the collecting duct in ARPKD; 2) alterations in cell polarity; and 3) changes in extracellular matrix composition. In addition to the renal cystic disease, ADPKD is associated with cyst formation in other epithelial organs, most notably the liver and pancreas, as well as connective tissue defects, such as intracranial aneurysms, aortic dissection, cardiac valve abnormalities, and abdominal wall hernias (116). In comparison, the ARPKD phenotype is expressed almost exclusively in the kidney and liver, with the latter lesion involving biliary dysgenesis a...

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“…As for liver lesions in human PKD, all cases of human ARPKD develop varying degrees of periportal fibrosis, bile ductual hyperplasia, and biliary dysgenesis 3,11 . Considering the rat PKD models, biliary cysts were not always observed in the chin and Han:SPRD rats 2,7,10,12 , but renal and biliary cysts always occurred concurrently in Crj:CD(SD) rats. The PKD of Crj:CD(SD) rats were due to dilatation of collecting ducts and always had the biliary cysts, thus the histological features of the kidneys and livers mostly resembled those of human ARPKD.…”

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confidence: 97%

“…The renal cysts derived from the collecting ducts progress very rapidly, and the rats die between the age of 6 and 11 months 2,6,7 . In addition to cystic lesions, chin rats suffer from skeletal abnormalities 7,8 . In contrast to chin rats, Han:SPRD rats, which have slowly progressive PKD 2 , are used as a model of human ADPKD.…”

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confidence: 99%

Polycystic Disease of the Kidney and Liver in Crj:CD(SD) Rats.

et al. 2001

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Polycystic lesions of kidney and liver were found in Crj:CD(SD) rats of 9 males and 6 females ranging in age from 5 to 57 weeks and were histopathologically or immunohistochemically investigated. Renal cysts were observed in the outer medulla at the beginning and confirmed to be dilatations of the collecting ducts by Dolichos biflorus agglutinin lectin histochemistry. At an advanced stage, the cysts expanded toward the cortex owing to dilatation of the collecting ducts and distal tubules, inflammatory cell infiltration, and fibrosis surrounding the cysts were observed additionally. The TUNEL assay revealed apoptotic cell death in the tubular epithelium of the cysts. Electron microscopy represented slightly thickened and laminated basement membranes of the cysts.The liver lesion at the beginning revealed slight dilatation of bile ducts and lymphatic ducts in Glisson's sheath. At the advanced stage, dilatation of bile ducts spread over the liver, proliferation of bile ducts, desquamation of the biliary epithelium, and fibrosis surroundings the bile ducts were observed in addition to the cystic lesions. The histological features of the cystic lesions were similar to those of human autosomal recessive polycystic kidney disease (PKD). None of the rat PKD models presented concurrently the biliary cysts. Therefore, these rats may be a potential model for human PKD and be useful for studying the correlation of the pathogenesis between the renal cysts and the biliary cyst. ( Laboratory animal models of human polycystic kidney disease (PKD) have been described in mice, rats, and other animal species 1, 2 . Two types of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), are known in humans 3 . Human ADPKD affects adults, and the renal cysts can be found at any locus of the nephron 3 . Cysts in other organs, including the liver, spleen, and pancreas have been described, but are not a consistent feature of the disease 3 . In contrast, human ARPKD affects children or juveniles, the renal cysts were predominantly localized in the collecting ducts, and biliary cysts are always seen in addition to renal cysts 3 . Though rat PKD models (e.g., Han:SPRD rats, chin rats) have been previously reported, biliary cysts were not always observed in these rat models 2 . Recently, a novel PKD model of rat was established in Crj:CD(SD) rats which have both renal and biliary cysts by continuous sibling mating 4 . We found PKD of the rats in drug-safety evaluation studies and describe the histological features of the rats in comparison with other rat PKD model, human ARPKD, and ADPKD. Sprague-Dawley rats were supplied by Charles River Japan Inc from 1992 till 1995. The animals were kept in a stainless steel cage at 22 ± 3°C room temperature, with 55 ± 15% relative humidity, 12:12 hours light:dark cycle, and an air exchange rate of 15 times per hour. All rats were given a standard CRF-1 diet (Oriental Yeast Co. Ltd., Tokyo, Japan) and chlorinated tap water ad libitum. A...

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A Mutant Rat with Congenital Skeletal Abnormalities and Polycystic Kidneys

Cited by 10 publications

References 7 publications

Autosomal Recessive Polycystic Kidney in Rats

Autosomal Recessive Polycystic Kidney in Rats

Murine models of polycystic kidney disease: molecular and therapeutic insights

Polycystic Disease of the Kidney and Liver in Crj:CD(SD) Rats.

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