Murine fumarylacetoacetate hydrolase (Fah) gene is disrupted by a neonatally lethal albino deletion that defines the hepatocyte-specific developmental regulation 1 (hsdr-1) locus

Journal Article · Sat Feb 15 00:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.4.1363· OSTI ID:5488169

Klebig, M L ^[1]; Russell, L B; Rinchik, E M ^[2]

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1. Univ. of Tennessee, Knoxville (United States) Oak Ridge National Lab., TN (United States)
2. Oak Ridge National Lab., TN (United States)

Homozygous deletion of the hepatocyte-specific developmental regulation 1 (hsdr-1) locus in mouse chromosome 7 results in perinatal death and a pleiotropic syndrome characterized by ultrastructural abnormalities of the liver and kidney, failure of induction of a number of specific transcription units in the liver and kidney during late gestation, and marked overexpression of an enzyme that defends against oxidative stress. Previously, the breakpoints of two albino (c) deletions (c{sup 14CoS} and c{sup IFAFyh}) that genetically define hsdr-1 were localized, on a long-range map, in the vicinity of the distal breakpoint of a viable albino deletion (c{sup 24R75M}) that breaks proximally within the c locus. Here the authors report the use of a probe derived from a deletion breakpoint fusion fragment cloned from c{sup 24R75M}/c{sup 24R75M} DNA to clone a breakpoint fusion fragment caused by the c{sup 14CoS} deletion. The proximal breakpoint of the c{sup 14CoS} deletion was discovered to disrupt a gene (Fah) encoding fumarylacetoacetate hydrolase, the last enzyme in the tyrosine degradation pathway. These mouse mutants may also provide models for the human genetic disorder hereditary tyrosinemia, which is associated with fumarylacetoacetate hydrolase deficiency and liver and kidney dysfunction.

• DOE Contract Number: AC05-84OR21400
• OSTI ID: 5488169
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 89:4; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HEREDITARY DISEASES
ETIOLOGY
HYDROLASES
GENE REGULATION
DNA-CLONING
HETEROCHROMOSOMES
KIDNEYS
LETHAL MUTATIONS
LIVER CELLS
MAN
MICE
TYROSINE
ULTRASTRUCTURAL CHANGES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BODY
CARBOXYLIC ACIDS
CHROMOSOMES
CLONING
DISEASES
DNA HYBRIDIZATION
ENZYMES
HYBRIDIZATION
HYDROXY ACIDS
MAMMALS
MORPHOLOGICAL CHANGES
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
550400* - Genetics