The Gunn rat
An accurate model of the disease, the Gunn rat, exists; the UGT1A1 gene in this strain carries a premature stop, leading to a very low UGT1A1 activity.
Charles Kenneth Gunn first discovered mutant rats in 1934 (published in 1938) in a Wistar rat colony maintained at the Connaught Laboratory in Toronto, Canada. Rats were jaundiced and the defect was transmitted as an autosomal recessive characteristic. It took several decades to fully elucidate at the molecular level the deficiency in the Gunn rats. The human counterpart of the disease was described by John Fielding Crigler and Victor Assad Najjar in 1952.
Various Gunn rat stocks were derived from those animals and have genetic contributions of different strains.
Gunn rats pups and adult animals (homozogous rats designed by jj) have a yellowish discoloration of the skin (jaundice).
Gunn rats are commercially available from Harlan, Indianapolis, Indiana. Gunn rats are also available from Japan SLC Inc..This animal model has been estremely valuable for the development of experimental treatments for the disease.
Recently, a mouse knock-out model (Ugt1-/- mice), in which the UGT1 locus has been disrupted has been created. In Ugt1-/- mice unconjugated levels of bilirubin are very high. These animals generally die within 2 weeks after birth.
Ugt1-/- pups are identified by their yellowish skin color as early as 12 hours after birth (from Nguyen et al., 2008).
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