A difference in mortality between two strains of jaundiced rats.
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 less than .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 less than .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 mumols/L, RHA/N-j = 248 mumols/L, P less than .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 less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)
Stobie
P E
PE
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Hansen
C T
CT
Hailey
J R
JR
Levine
R L
RL
D000818:Animals; D001663:Bilirubin / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D007565:Jaundice / Q000235:genetics* / Q000378:metabolism; D007647:Kernicterus / Q000209:etiology; D015993:Life Tables; D008099:Liver / Q000201:enzymology; D008297:Male; D011689:Purkinje Cells / Q000473:pathology; D051381:Rats; D011912:Rats, Inbred ACI; D012709:Serum Albumin / Q000378:metabolism; D013045:Species Specificity; D015996:Survival Rate
D012709:Serum Albumin; D014453:Glucuronosyltransferase; D001663:Bilirubin