| First Author | Kelsey G | Year | 1992 |
| Journal | J Cell Sci Suppl | Volume | 16 |
| Pages | 117-22 | PubMed ID | 1297646 |
| Mgi Jnum | J:4991 | Mgi Id | MGI:53470 |
| Doi | 10.1242/jcs.1992.supplement_16.14 | Citation | Kelsey G, et al. (1992) Multiple effects on liver-specific gene expression in albino lethal mice caused by deficiency of an enzyme in tyrosine metabolism. J Cell Sci Suppl 16:117-22 |
| abstractText | alf/hsdr-1 is a locus in the mouse defined by albino deletions to be essential for neonatal viability. Homozygous deletion of alf/hsdr-1 leads to a pleiotropic phenotype in liver and kidney, including impaired perinatal activation of hormone-dependent genes, and the induction of detoxifying enzymes and early-response genes. To elucidate the molecular basis of this complex phenotype, we have identified the gene mapping at alf/hsdr-1 by positional cloning, using overlapping albino locus deletions to define the location of alf/hsdr-1. The gene encodes fumarylacetoacetate hydrolase, FAH, an enzyme of tyrosine metabolism. Genetically determined FAH deficiency in man leads to a severe liver failure in infants. In mice, we find that the normal sites of expression of FAH correlate tightly with cell-types which display abnormalities in albino lethal mice. The identification of the Fah gene as a candidate for alf/hsdr-1 offers a novel explanation for the complex phenotype, one into which all aspects can be accommodated. The phenotype can now be understood as a sequence of responses to toxic electrophilic metabolites. |
