E-GEOD-41044 - MethylMalonic Acidemia (MMA) is predicted by lipocalin-2 (LCN2) and attenuated by antioxidant therapy

Released on 1 May 2013, last updated on 7 May 2013
Mus musculus
Samples (12)
Array (1)
Protocols (6)
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
Experiment type
transcription profiling by array 
abdel elkahloun <abdel@mail.nih.gov>, Abdel G Elkahloun, Charles P Venditti, Irini Manoli, Justin R Sysol
Investigation descriptionE-GEOD-41044.idf.txt
Sample and data relationshipE-GEOD-41044.sdrf.txt
Raw data (1)E-GEOD-41044.raw.1.zip
Processed data (1)E-GEOD-41044.processed.1.zip
Array designA-AFFY-130.adf.txt