| First Author | Leandro J | Year | 2021 |
| Journal | Mol Genet Metab | Volume | 132 |
| Issue | 2 | Pages | 139-145 |
| PubMed ID | 33483254 | Mgi Jnum | J:321541 |
| Mgi Id | MGI:6884601 | Doi | 10.1016/j.ymgme.2021.01.004 |
| Citation | Leandro J, et al. (2021) Glutaric aciduria type 3 is a naturally occurring biochemical trait in inbred mice of 129 substrains. Mol Genet Metab 132(2):139-145 |
| abstractText | 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 Sugct(129/129) 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. |
