| Experiment Id | E-GEOD-41044 | Series Id | GSE41044 |
| Name | MethylMalonic Acidemia (MMA) is predicted by lipocalin-2 (LCN2) and attenuated by antioxidant therapy | Experiment Type | transcription profiling by array |
| Study Type | WT vs. Mutant | Source | ArrayExpress |
| Curation Date | 2019-01-15 |
| description | Isolated methylmalonic acidemia (MMA) is a pleiotropic enzymatic defect of branched-chain amino acid oxidation most commonly caused by deficiency of methylmalonyl-CoA mutase (MUT). End stage renal disease (ESRD) is emerging as an inevitable disease-related complication, recalcitrant to conventional therapies and liver transplantation. To establish a viable model of MMA-associated renal disease, methylmalonyl-CoA mutase (Mut) was expressed in the liver of Mut -/- mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut -/- ;TgINS-Alb-Mut mice were rescued from the neonatal lethality displayed by Mut -/- mice and manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstital nephritis (CTIN) and prominent ultrastructural changes in the proximal tubular mitochondria, replicating precisely the renal manifestations seen in a large MMA patient cohort. To explore the pathophysiological changes that underlie the renal disease of MMA, we compared gene expression profiles of whole kidney mRNA samples between 4 female Mut +/+, Mut +/- and Mut -/- ;TgINS-Alb-Mut mice after they ingested a HP diet for 2 months. Females were used because more survived the dietary challenge, whereas the histology, ultrastructure and GFR effects were identical between sexes |
