A difference in mortality between two strains of jaundiced rats

Area of Science:

• Genetics
• Animal Models
• Biochemistry

Background:

• Homozygous Gunn rats, lacking bilirubin glucuronyltransferase, serve as a model for neonatal hyperbilirubinemia and kernicterus.
• The Gunn mutation (j) causes jaundice due to impaired bilirubin conjugation.

Purpose of the Study:

• To develop and characterize two new inbred rat strains carrying the Gunn mutation.
• To compare the phenotypes, mortality, and incidence of kernicterus in these new strains.

Main Methods:

• Breeding mutant Gunn gene (j) into RHA/N and ACI/N rat strains to create RHA/N-j and ACI/N-j lines.
• Liver assays to confirm absence of transferase activity.
• Monitoring mortality, kernicterus signs (ataxia), serum bilirubin, and albumin concentrations through 8 weeks of age.

Main Results:

• Both RHA/N-j and ACI/N-j strains confirmed absence of transferase activity.
• RHA/N-j rats showed low mortality (20%) comparable to non-jaundiced littermates.
• ACI/N-j rats exhibited significantly higher mortality (81% vs 34%) and frequent kernicterus (73% vs 11%) compared to RHA/N-j.
• Serum bilirubin and albumin levels were comparable, with a higher bilirubin-to-albumin ratio at 20 days in ACI/N-j rats.

Conclusions:

• The RHA/N-j rat strain provides a valuable model for neonatal hyperbilirubinemia with minimal mortality and no kernicterus.
• The ACI/N-j rat strain presents a model with high incidence of kernicterus and mortality, useful for studying severe hyperbilirubinemia.
• These distinct strains offer differential models for investigating the pathogenesis and treatment of hyperbilirubinemia.