Expression of the Wilson disease gene is deficient in the Long-Evans Cinnamon rat.
Long-Evans Cinnamon rats develop a necrotizing hepatitis characterized by excessive hepatic copper accumulation, defective holoceruloplasmin biosynthesis and impaired biliary copper excretion. To elucidate the molecular basis of this defect, a cDNA clone encoding the rat Wilson disease gene was isolated and used to examine gene expression in selected tissues from normal and Long-Evans Cinnamon rats. Although this cDNA readily detects Wilson transcripts in liver and other tissues from normal rats, such transcripts are entirely absent from tissues derived from the Long-Evans Cinnamon rat strain. These data therefore identify the Long-Evans Cinnamon rat as the first bona fide animal model of Wilson disease and suggest that this rat strain may be a valuable resource in the study of this genetic disorder.
Yamaguchi
Y
Y
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Heiny
M E
ME
Shimizu
N
N
Aoki
T
T
Gitlin
J D
JD
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D011922:Rats, Mutant Strains; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D027682:Cation Transport Proteins; D018076:DNA, Complementary; D003300:Copper; D000251:Adenosine Triphosphatases; C486202:Atp7a protein, rat; D000073840:Copper-Transporting ATPases