Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA175609 | ENA |
REPOSITORIES: ENA
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Project 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
2013-05-01 | E-GEOD-41044 | biostudies-arrayexpress
Project 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.
2013-05-01 | GSE41044 | GEO
Project description:Methylmalonic acidemia (MMA) is one of the most common inherited metabolic disorders, due to deficiency of the mitochondrial methylmalonyl ̶ coenzyme A mutase (MUT). How MUT deficiency triggers mitochondrial alterations and cell damage remains unknown, preventing the development of disease-modifying therapies. To assess the effect of MUT deficiency on gene expression we investigated the transcriptome of in kidney cells derived from healthy controls or patients with MMA who harbor inactivating mutations in MUT. Microarray data indicate that MUT deficiency induces a profound and global change in gene expression that may be in part responsible of cellular alterations observed in patient cells.
2019-10-01 | GSE120683 | GEO
Project description:Methylmalonic acidemia (MMA), an organic acidemia characterized by metabolic instability and multiorgan complications, is most frequently caused by mutations in methylmalonyl-CoA mutase (MUT). To define the metabolic adaptations in MMA, in the chronic and acute settings, we studied a mouse model generated by transgenic expression of Mut in the muscle. Mut-/-;TgINS-MCK-Mut mice accurately replicate the hepato-renal mitochondriopathy and growth failure seen in severely affected patients, and were used to characterize the response to fasting. The hepatic transcriptome in MMA mice was characterized by the chronic activation of stress-related pathways and responded abberrantly to fasting when compared to controls.
2019-08-01 | GSE118862 | GEO
Project description:In diabetes, the kidney contributes to the development of diabetic hyperglycemia by increasing glucose reabsorption from the primary urine and by upregulating gluconeogenesis in the proximal tubule. However, these two processes are also controlled by the circadian clock, a mechanism that synchronizes a large number of specific renal functions with environmental daily cycles. Here, we investigated the (patho)physiological role of intrinsic renal tubule circadian clocks in the diabetic kidney. We demonstrate that diabetic mice devoid of the circadian transcriptional regulator BMAL1 in the renal tubule exhibit additional enhancement of renal gluconeogenesis, exacerbated hyperglycemia, increased glucosuria, polyuria and renal hypertrophy. Collectively, our results suggest that diabetic hyperglycemia can be worsened by dysfunction or misalignment of intrinsic renal circadian clocks.
2022-05-27 | GSE178319 | GEO
Project description:Intrinsic TGF-b Signaling Attenuates Proximal Tubule Mitochondrial Injury and Inflammation in Chronic Kidney Disease
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Project description:Dent disease has multiple defects attributed to proximal tubule malfunction including low molecular weight proteinuria, aminoaciduria, phosphaturia and glycosuria. In order to understand the changes in kidney function of the Clc5 transporter gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal tubules of mouse kidneys. Overall 720 genes are expressed differentially in the proximal tubules of the Dent Clcn5 knockout mouse model compared to those of control wild type mice. The fingerprint of these gene changes may help us to understand the phenotype of Dent disease. Experiment Overall Design: Renal proximal tubules were dissected from wild type and Clcn5 knockout mice. Mice were anesthetized with halothane, the abdominal aorta of each animal was accessed and the left kidney was perfused with an ice-cold salt. Proximal tubule dissection was performed in an ice-cold salt solution. After dissection of approximately 80-100 segments of 2 mm in length per kidney, the RNA for 3-4 mice was combined to have enough RNA per chip. Experiment Overall Design: 3 microarrays each of wild type and knockout mouse proximal tubule were processed
2008-06-11 | E-GEOD-10162 | biostudies-arrayexpress
Project description:To assess differential gene expression by APOL1 renal-risk (2 risk alleles) vs. non-risk (G0G0) genotypes in primary proximal tubule cells (PTCs), global gene expression (mRNA) levels were examined on Affymetrix HTA 2.0 arrays in primary PTCs cultured from non-diseased kidney in African Americans without CKD who underwent nephrectomy for localized renal cell carcinoma. To detect differentially expressed gene profiles attributable to APOL1 renal-risk genotypes, African American primary proximal tubule cells with two APOL1 renal-risk alleles (N=5) and lacking renal-risk alleles (N=25) were included in comparisons of global gene expression.
2016-08-23 | E-GEOD-85920 | biostudies-arrayexpress