title: Developmental study of hepatic glutamine synthetase in a mouse model of congenital hyperammonemia.
abstract: The development of hepatic glutamine synthetase (GS; EC 6.3.1.2) activity and expression was studied in 1 to 112 day old sparse-fur (spf) mutant mice, with X-linked ornithine transcarbamylase (OTC, EC 2.1.3.3.) deficiency. The spf/Y mutant mice were found to have a smaller body weight (p < 0.01) yet possessed a larger liver (p < 0.01-0.05) in comparison to normal male mice (+/Y). The neonatal hepatic GS activity was retarded in the spf/Y mice (p < 0.01) but reached normal values by the 28th day of age, after which it increased as compared to the control CD-I mice (p < 0.01). The spf GS activity remained constant from 28 to 56 days, whereas the CD-I GS activity decreased. A further significant increase in the spf GS activity was observed from 56 day to 112 day indicating its adaptation. The decrease of GS mRNA in the spf/Y mice from 28 to 112 days of age (3.72 +/- 0.25 vs 1.68 +/- 0.32, p < 0.01) suggests translational and post-translational modifications in the regulation of GS activity. The changes in the activity and expression patterns of GS could be due to an effect of the OTC mutation on the hepatic ammonia metabolism. This may be indicative of the adaptational processes in the spf mutant mice, which may play a specific role in this animal model to help it to survive with its hyperammonemia.
authors.affiliation: Department of Pediatrics, University of Montreal and Pediatric Research Center, Sainte-Justine Hospital, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Skarpetas
authors.forename: Y
authors.initials: Y
authors.lastname: Mawal
authors.forename: I A
authors.initials: IA
authors.lastname: Qureshi
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology*; D000641:Ammonia / Q000097:blood* / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase