Glutaric aciduria type 3 is a naturally occurring biochemical trait in inbred mice of 129 substrains.
The glutaric acidurias are a group of inborn errors of metabolism with different etiologies. Glutaric aciduria type 3 (GA3) is a biochemical phenotype with uncertain clinical relevance caused by a deficiency of succinyl-CoA:glutarate-CoA transferase (SUGCT). SUGCT catalyzes the succinyl-CoA-dependent conversion of glutaric acid into glutaryl-CoA preventing urinary loss of the organic acid. Here, we describe the presence of a GA3 trait in mice of 129 substrains due to SUGCT deficiency, which was identified by screening of urine organic acid profiles obtained from different inbred mouse strains including 129S2/SvPasCrl. Molecular and biochemical analyses in an F2 population of the parental C57BL/6J and 129S2/SvPasCrl strains (B6129F2) confirmed that the GA3 trait occurred in Sugct129/129 animals. We evaluated the impact of SUGCT deficiency on metabolite accumulation in the glutaric aciduria type 1 (GA1) mouse model. We found that GA1 mice with SUGCT deficiency have decreased excretion of urine 3-hydroxyglutaric acid and decreased levels glutarylcarnitine in urine, plasma and kidney. Our work demonstrates that SUGCT contributes to the production of glutaryl-CoA under conditions of low and pathologically high glutaric acid levels. Our work also highlights the notion that unexpected biochemical phenotypes can occur in widely used inbred animal lines.
['Leandro|João|J|', 'Bender|Aaron|A|', 'Dodatko|Tetyana|T|', 'Argmann|Carmen|C|', 'Yu|Chunli|C|', 'Houten|Sander M|SM|']
D000217:Acyltransferases D000592:Amino Acid Metabolism, Inborn Errors D000818:Animals D004195:Disease Models, Animal D005977:Glutarates D006801:Humans D008239:Lysine D008659:Metabolic Diseases D051379:Mice D008815:Mice, Inbred Strains D010088:Oxidoreductases D010641:Phenotype D014166:Transferases
Glutaric aciduria Glutaric acid Inbred mouse strains Lysine Mouse genetics