Chromosomal deletions around the albino locus in the mouse cause loss of hormone-inducible expression of the unlinked structural gene encoding cytosolic aspartate aminotransferase.
A group of genes in the mouse encoding liver-specific gluconeogenic enzymes and mapping on different chromosomes lose their normal competence for hormone-inducible expression in animals homozygous for chromosomal deletions around the albino locus on chromosome 7. The basal expression of these same genes remains normal. In previous investigations, glucocorticoid hormones as well as their receptors were found to be normal in the deletion homozygotes. The results reported here identify an additional unlinked structural gene whose regulation appears to be affected by the deletions--i.e., that encoding cytosolic aspartate aminotransferase, a housekeeping gene that participates in gluconeogenesis in the liver. In normal mice, its mRNA level increases sharply at birth, specifically in the liver, and can be increased even further by dexamethasone and cAMP treatment. These increases fail to occur in mice homozygous for the specific deletions in chromosome 7. Interestingly, prenatally at 18-19 days of gestation, the gene is expressed at the same basal level in liver and brain of both normal and mutant mice. These observations strengthen the evidence implicating the deleted gene(s) as an essential factor(s) in the normal mechanisms of hormone-inducible expression of particular unlinked structural genes.
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.
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Barouki
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Waelsch
D000417:Albinism / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001219:Aspartate Aminotransferases / Q000096:biosynthesis / Q000235:genetics*; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D002872:Chromosome Deletion; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D005838:Genotype; D008099:Liver / Q000737:chemistry / Q000196:embryology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
D012333:RNA, Messenger; D003907:Dexamethasone; D000242:Cyclic AMP; D001219:Aspartate Aminotransferases