Polycystic kidney disease gene in the Lewis polycystic kidney rat is mapped to chromosome 10q21&amp;ndash;q26

Yengkopiong, Jada Pasquale

doi:10.2147/agg.s32913

Cited by 2 publications

(24 citation statements)

References 55 publications

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“…The current work is a further extension of the study in which a genome-wide linkage scan analysis identified a mutation in the Nek8 gene as the cause of NPHP in LPK rats [10,25,31]. It is now reported that this mutation is influenced by genetic modifier loci in the non-mutant, female WKY rats.…”

Section: Introductionmentioning

confidence: 77%

“…However, the pathogenesis of the classical ARP-KD is caused by mutations only in the Pkhd1 gene, which was mapped to human chromosome 6p21.1-p12 [6], and in murine models, the orthologs are intermittently located in different chromosomes [7,8,9]. Like NPHP, ARPKD is also characterized by mul-tiple fluid-filled cystic kidneys, anemia, hypertension and eventually end stage renal disease [10].…”

Section: Introductionmentioning

confidence: 99%

“…The disorders also have common clinical presentation, which include infantile incidence, renal failure, anemia, polyuria without hematuria, proteinuria and hypertension [10,16]. It has, however, become clearer that the variability of disease phenotypes, especially the progression and extrarenal manifestation, is a feature common to both NPHP and ARPKD.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we carried out a rigorous study to elucidate the molecular pathogenesis and inheritance of NPHP in Lewis polycystic kidney (LPK) rats, and the quantitative trait locus (QTL) responsible for the disease phenotypes was mapped to chromosome 10q21-q26 [10]. The QTL contains genes that are important in signal transduction, cell growth, cell proliferation and cell differentiation [20,21], and they were also associated with unregulated cell proliferation and cancer [22,23,24].…”

Section: Introductionmentioning

confidence: 99%

“…Mating experiments between male and female progeny with enlarged cystic kidneys produced 100% pups with bilaterally enlarged, fluid-filled cystic kidneys [10]. This colony is now called the Lewis polycystic kidney (LPK/SsNArc +/+ ) rats.…”

Section: Introductionmentioning

confidence: 99%

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Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats

Yengkopiong¹,

Lako²

2015

pjp

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Genetic modifier loci influence the inheritance of diseases and lead to variability in phenotype progression. We report the influence of modifier loci in female Wistar Kyoto (WKY) rats on cellular pathogenesis of nephronophthisis inherited from Lewis polycystic kidney (LPK) rats. The loci modified cellular expression and progression of nephronophthisis in the backcross 1 (BC1) progeny. Mating experiments to produce BC1 progeny were carried out between three male LPK and seven female WKY rats. Fifteen female rats from the F1 generation were mated with the male LPK rats to produce the BC1 progeny. The rats with cystic kidney disease were identified and histology of the kidneys was carried out. Mapping studies and linkage analysis were carried out to identify the modifier loci. The BC1 progeny were less affected than the LPK strain with respect to disease severity and progression of the kidneys to end stage renal disease. It was found that the mean values of all the disease phenotypes of the mutant BC1 progeny were significantly different from those of the LPK rats, and these segregated with the genotypes of the markers located on chromosomes 5q34-q36 and 7q11-q34, giving maximum LOD scores greater than 3 (p < 0.001).

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Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats

Yengkopiong¹,

Lako²

2015

pjp

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Genetic background of nonmutant Piebald-Virol-Glaxo rats does not influence nephronophthisis phenotypes

Yengkopiong¹,

Lako²

2013

IJNRD

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BackgroundNephronophthisis (NPHP), which affects multiple organs, is a hereditary cystic kidney disease (CKD), characterized by interstitial fibrosis and numerous fluid-filled cysts in the kidneys. It is caused by mutations in NPHP genes, which encode for ciliary proteins known as nephrocystins. The disorder affects many people across the world and leads to end-stage renal disease. The aim of this study was to determine if the genetic background of the nonmutant female Piebald-Virol-Glaxo (PVG/Seac–/–) rat influences phenotypic inheritance of NPHP from mutant male Lewis polycystic kidney rats.MethodsMating experiments were performed between mutant Lewis polycystic kidney male rats with CKD and nonmutant PVG and Wistar Kyoto female rats without cystic kidney disease to raise second filial and backcross 1 progeny, respectively. Rats that developed cystic kidneys were identified. Systolic blood pressure was determined in each rat at 12 weeks of age using the tail and cuff method. After euthanasia, blood samples were collected and chemistry was determined. Histological examination of the kidneys, pancreas, and liver of rats with and without cystic kidney disease was performed.ResultsIt was established that the genetic background of nonmutant female PVG rats did not influence the phenotypic inheritance of the CKD from mutant male Lewis polycystic kidney rats. The disease arose as a result of a recessive mutation in a single gene (second filial generation, CKD = 13, non-CKD = 39, χ2 = 0.00, P ≥ 0.97; backcross 1 generation, CKD = 67, non-CKD = 72, χ2 = 0.18, P > 0.05) and inherited as NPHP. The rats with CKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia, but there were no extrarenal cysts and disease did not lead to early pup mortality.ConclusionThe genetic background of the nonmutant PVG rats does not influence the genetic and phenotypic inheritance of CKD from mutant Lewis polycystic kidney rats. A single recessive mutation incapacitated the gene, which relaxed its functional constraints, and led to formation of multiple cysts in the kidneys of the homozygous mutant rats.

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Polycystic kidney disease gene in the Lewis polycystic kidney rat is mapped to chromosome 10q21–q26

Cited by 2 publications

References 55 publications

Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats

Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats

Genetic background of nonmutant Piebald-Virol-Glaxo rats does not influence nephronophthisis phenotypes

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