title: Disruption of the adenosine deaminase gene causes hepatocellular impairment and perinatal lethality in mice.
abstract: We have generated mice with a null mutation at the Ada locus, which encodes the purine catabolic enzyme adenosine deaminase (ADA, EC 3.5.4.4). ADA-deficient fetuses exhibited hepatocellular impairment and died perinatally. Their lymphoid tissues were not largely affected. Accumulation of ADA substrates was detectable in ADA-deficient conceptuses as early as 12.5 days postcoitum, dramatically increasing during late in utero development, and is the likely cause of liver damage and fetal death. The results presented here demonstrate that ADA is important for the homeostatic maintenance of purines in mice.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wakamiya
authors.forename: M R
authors.initials: MR
authors.lastname: Blackburn
authors.forename: R
authors.initials: R
authors.lastname: Jurecic
authors.forename: M J
authors.initials: MJ
authors.lastname: McArthur
authors.forename: R S
authors.initials: RS
authors.lastname: Geske
authors.forename: J
authors.initials: J
authors.lastname: Cartwright
authors.forename: K
authors.initials: K
authors.lastname: Mitani
authors.forename: S
authors.initials: S
authors.lastname: Vaishnav
authors.forename: J W
authors.initials: JW
authors.lastname: Belmont
authors.forename: R E
authors.initials: RE
authors.lastname: Kellems
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D005260:Female; D005804:Genes, Lethal; D005838:Genotype; D005865:Gestational Age; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D006706:Homeostasis; D007962:Leukocytes / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D011247:Pregnancy; D011687:Purines / Q000378:metabolism; D015183:Restriction Mapping
chemical_list: D003838:Deoxyadenine Nucleotides; D011687:Purines; D000255:Adenosine Triphosphate; D000243:Adenosine Deaminase; C026600:2'-deoxyadenosine triphosphate