Metabolic studies in a mouse model of hepatorenal tyrosinemia: absence of perinatal abnormalities.
Radiation induced chromosomal deletions at the albino locus in the mouse, lethal when homozygous, cause abnormalities of expression of several unlinked liver specific genes. Recently, the gene encoding FAH was shown to be included in the deletions. Since in humans FAH mutations cause tyrosinemia type I, deletion homozygous mice were suspected of having tyrosinemia. Studies of plasma amino acids did not confirm this suspicion. Also, succinylacetone levels were normal in fetal and newborn livers of deletion homozygotes. The present evidence, therefore, does not support the assumption that the earlier described ultrastructural and enzyme abnormalities in deletion homozygotes are secondary effects of tyrosinemia caused by the deletion of FAH.
Collins
J C
JC
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461.
Buchanan
D N
DN
Thoene
J G
JG
Erickson
R P
RP
Brooks
S S
SS
Gluecksohn-Waelsch
S
S
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D002872:Chromosome Deletion; D004195:Disease Models, Animal; D006537:Heptanoates / Q000378:metabolism; D006720:Homozygote; D006867:Hydrolases / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D014443:Tyrosine / Q000097:blood*
D006537:Heptanoates; D014443:Tyrosine; C020804:succinylacetone; D006867:Hydrolases; C020156:fumarylacetoacetase