1 From the Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, and the Veterinary Resources Branch, National Institutes of Health, Bethesda, MD; the Walter Reed Army Institute of Research, Washington, DC; and the Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda
Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. Two new, inbred rat strains that carry the Gunn mutation are described. These were developed by breeding the mutant Gunn gene (j) into the RHA/N and ACI/N strains, producing the new lines, which were designated RHA/N-j and ACI/N-j. Liver assay confirmed the absence of transferase activity in jaundiced rats from both of the new strains, but marked differences in mortality between the strains were observed. The mortality of jaundiced RHA/N-j rats through 8 weeks was the same as that of their nonjaundiced littermates (20%). In contrast, mortality of jaundiced ACI/N-j rats was distinctly greater than that of their nonjaundiced littermates (81% vs 34%, P < .001). Signs of kernicterus such as ataxia were much more frequent in jaundiced ACI/N-j rats than in jaundiced RHA/N-j rats (73% vs 11%, P < .001). Both strains had comparable albumin concentrations through 8 weeks of age. Serum bilirubin concentrations were also comparable, except for a small but significant difference at 20 days of age (ACI/N-j = 294 µmol/L, RHA/N-j = 248 µmol/L, P < .01). Similarly, the bilirubin-to-albumin ratios were comparable except for a significantly higher ratio at 20 days of age in the ACI/N-j rats (ACI/N-j = 0.70, RHA/N-j = 0.51, P < .01). Thus, the RHA/N-j strain is unusual in that the jaundiced animals remain healthy. Conversely, the ACI/N-j animals demonstrate a high incidence of kernicterus with mortality. This dramatic strain difference implies that factors in addition to deficiency of bilirubin glucuronyltransferase are modulating the susceptibility to bilirubin toxicity.
Key Words: bilirubin kernicterus Gunn rats jaundice
Submitted on September 5, 1989
Accepted on February 28, 1990
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