Glucocorticoid-induced polycystic kidney disease--a threshold trait

Area of Science:

• Nephrology
• Toxicology
• Genetics

Background:

• Polycystic kidney disease (PKD) is a complex genetic disorder.
• Understanding the genetic and environmental factors contributing to PKD is crucial for developing effective treatments.
• Hydrocortisone acetate is a synthetic corticosteroid with known biological effects.

Purpose of the Study:

• To investigate the induction of polycystic kidney disease (PKD) in inbred mouse strains using hydrocortisone acetate.
• To determine the genetic and environmental influences on PKD susceptibility and severity.
• To characterize PKD as a multifactorial threshold trait.

Main Methods:

• Administration of hydrocortisone acetate (250 mg/kg) to newborn mice across 18 inbred strains.
• Histological examination and semi-continuous grading (0 to 4+) of kidney cyst formation.
• Quantitative analysis using maximum likelihood methods to estimate liability distributions and thresholds.

Main Results:

• Hydrocortisone acetate induced varying degrees of PKD in all 18 mouse strains; controls remained unaffected.
• A significant environmental effect related to drug source was identified.
• Strain-specific thresholds for PKD ranged from 0.94 to -0.71, with three distinct susceptibility groups observed.
• PKD was confirmed as a multifactorial threshold trait, influenced by genetic, environmental, and random factors.

Conclusions:

• Hydrocortisone acetate administration is a viable method for inducing PKD in mice, allowing for the study of genetic and environmental influences.
• Susceptibility to drug-induced PKD is a complex trait influenced by multiple genetic and environmental factors.
• The findings support a multifactorial model for PKD, highlighting the interplay between genetic predisposition and environmental triggers.