Glucocorticoid-induced polycystic kidney disease: a threshold trait

A. T.J. McDonald; J. F.S. Crocker; S. C. Digout; S. C. McCarthy; S. R. Blecher; D. E.C. Cole

doi:10.1038/ki.1990.64

Glucocorticoid-induced polycystic kidney disease: a threshold trait

A. T.J. McDonald, J. F.S. Crocker, S. C. Digout, S. C. McCarthy, S. R. Blecher, D. E.C. Cole

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57Bl/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait.

Original language	English
Pages (from-to)	901-908
Number of pages	8
Journal	Kidney International
Volume	37
Issue number	3
DOIs	https://doi.org/10.1038/ki.1990.64
Publication status	Published - 1990
Externally published	Yes

Bibliographical note

Funding Information:
The work was supported by a grant from the Medical Research Council of Canada. We thank Karen Morash, Maureen McGuire-Grandy, and Heather Gillis for assistance in the preparation of the

ASJC Scopus Subject Areas

Nephrology

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10.1038/ki.1990.64

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title = "Glucocorticoid-induced polycystic kidney disease: a threshold trait",

abstract = "Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57Bl/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait.",

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note = "Funding Information: The work was supported by a grant from the Medical Research Council of Canada. We thank Karen Morash, Maureen McGuire-Grandy, and Heather Gillis for assistance in the preparation of the",

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T2 - a threshold trait

AU - McDonald, A. T.J.

AU - Crocker, J. F.S.

AU - Digout, S. C.

AU - McCarthy, S. C.

AU - Blecher, S. R.

AU - Cole, D. E.C.

N1 - Funding Information: The work was supported by a grant from the Medical Research Council of Canada. We thank Karen Morash, Maureen McGuire-Grandy, and Heather Gillis for assistance in the preparation of the

PY - 1990

Y1 - 1990

N2 - Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57Bl/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait.

AB - Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57Bl/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait.

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Glucocorticoid-induced polycystic kidney disease: a threshold trait

Abstract

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ASJC Scopus Subject Areas

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