Analysis Tools
mortality/aging
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• Background Sensitivity: mice die shortly after birth unlike on a mixed 129S/SvEv, C57BL/6, and FVB/N background where a few mice survive weaning
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Allele Symbol Allele Name Allele ID |
Mmuttm1Cpv targeted mutation 1, Charles P Venditti MGI:3840300 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: mice die shortly after birth unlike on a mixed 129S/SvEv, C57BL/6, and FVB/N background where a few mice survive weaning
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• few mice survive post-weaning
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• Background Sensitivity: a few mice survive post-weaning whereas no mice survive weaning on a congenic C57BL/6 background
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• levels of plasma methylmalonic acid are higher than in wild-type mice
• mice exhibit a decrease in free carnitine, valine, isoleucine, and orinthine, and elevated propionylcarnitine and alanine compared to in wild-type mice
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• mice exhibit a decrease in free carnitine, valine, isoleucine, and orinthine, and elevated propionylcarnitine and alanine compared to in wild-type mice
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• in one ill mouse, the urine organic acid content is increased compared to in wild-type mice
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• in older mice, pancreatic cells show megamitochondria compared to in wild-type cells
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• in older mice, exocrine pancreatic cells exhibit fewer zymogen granules than in wild-type cells
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• in older mice, beta cells have fewer insulin granules than in wild-type cells
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• in one ill mouse, the urine organic acid content is increased compared to in wild-type mice
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• tubulointerstitial inflammation in older mice
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• beginning on day 7, cells within the proximal convoluted tubules exhibit megamitochondria with underdeveloped cristae and peculiar lamellations unlike in wild-type cells
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• hepatocyte mitochondrial become enlarged and exhibit dysmorphic cristae, intramitochondrial lamellar inclusion body formation, and a less electron-dense matrix compared to in wild-type cells
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• the number and size of lipid droplets in hepatocytes is increased compared to in wild-type mice
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• hepatocyte mitochondrial become enlarged and exhibit dysmorphic cristae, intramitochondrial lamellar inclusion body formation, and a less electron-dense matrix compared to in wild-type cells
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• citrate synthase activity is decreased in hepatocytes compared to in wild-type cells
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• complex I + III and complex II + III activities are decreased in hepatocytes compared to in wild-type cells
• COX activity is decreased more than 50% in hepatocytes compared to in wild-type cells
• however, mitochondrial function in skeletal muscle and whole kidney samples is normal
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• mice weigh 66%, 67%, 69%, and 51% of wild-type at 6, 14, 18, and 230 days, respectively
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• early and significant
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• in older mice, exocrine pancreatic cells exhibit fewer zymogen granules than in wild-type cells
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• tubulointerstitial inflammation in older mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die between 24 and 36 hours after birth with respiratory distress
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• at E16.5 and in newborn mice, levels of plasma methylmalonic acid are higher than in wild-type mice
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• at 8 to 12 hours of age, mice exhibit methylmalonic acidemia unlike wild-type mice
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• 24 hours after birth, mice exhibit a reduction in the stomach milk spot and dehydration unlike wild-type mice
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• at 8 to 12 hours of age, mice exhibit methylmalonic aciduria unlike wild-type mice
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• in 2 of 8 mice
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• 24 and 36 hours after birth
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• at 24 to 36 hours after birth, mice exhibit non-necrotic lipidotic changes in the liver unlike in wild-type mice
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• the brain appears compressed against the dura mater unlike in wild-type mice
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• at 8 to 12 hours of age, mice exhibit methylmalonic aciduria unlike wild-type mice
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• in 2 of 8 mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | DOID:0060740 |
OMIM:251000 |
J:147338 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Enlarged mitochondria with whorl-like cristae in Mmuttm1Cpv/Mmuttm1Cpv Tg(Alb-Mut)#Cpv/0 mice fed a high-protein diet
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• mice fed a high-protein diet at the age of 2-3 months for 2 months show a 52% survival rate, with males more severely affected
• males fed a high-protein diet rarely survive beyond 2 months of age
• treatment of mice fed a high-protein diet with the antioxidant, ubiquinone, improves survival
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• females fed a high-protein (casein) diet exhibit rapid weight loss of 14% within the first month and fail to regain weight
• treatment of mice fed a high-protein diet with the antioxidant, ubiquinone, decreases weight loss
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• males, but not females, fed a high-protein diet for 2 months exhibit an increase in serum creatinine
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• elevation in plasma methylmalonic acid levels
• females fed a high-protein diet exhibit increased plasma methylmalonic acid levels
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• males fed a regular diet exhibit lower plasma bicarbonate levels
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• mice on a high-protein diet for 2 months exhibit increased plasma Lcn2 (lipocalin-2) levels, a biomarker for renal dysfunction and oxidative stress
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• males fed a regular diet exhibit higher plasma chloride concentrations
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• males fed a regular diet exhibit lower plasma bicarbonate and higher plasma chloride levels indicating chronic hyperchloremic metabolic acidosis, however urinary ammonium excretion is not increased
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• females fed a high-protein diet for 6 months develop severe multifocal tubulointerstitial nephritis, with a granular kidney cortex appearance, and fine microvesicular cytoplasmic changes in the convoluted proximal segment tubules
• however, glomeruli appear normal and podocyte foot processes are not effaced in mice fed a high-protein diet for 6 months
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• females fed a high-protein diet for 6 months exhibit a large number of mitochondria in the kidneys with electron-dense matrix and abnormal cristae in the proximal tubules
• however, kidneys appear histologically normal after 2 months on a high-protein diet
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• multiple matrix granules/deposits in the renal tubular cytosol
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• mice fed a high-protein diet for 2 months show a reduction in glomerular filtration rate compared to heterozygous controls or mutants on a regular diet
• single-nephron glomerular filtration rate is lower in males fed a regular diet
• whole-body glomerular filtration rate in mice fed a regular diet is not decreased until 9-12 months of age
• treatment of mice fed a high-protein diet with the antioxidant, ubiquinone, improves glomerular filtration rate
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• diminution of the proximal tubule fluid reabsorption rate in males fed a regular diet, however males also show a lower fractional fluid reabsorption, indicating reduced reabsorptive capacity of the proximal tubule independent of glomerular filtration rate
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• females fed a high-protein diet for 6 months exhibit a large number of mitochondria in the kidneys with electron-dense matrix and abnormal cristae in the proximal tubules
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• females fed a high-protein diet for 6 months exhibit a large number of mitochondria in the kidneys with electron-dense matrix and abnormal cristae in the proximal tubules
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• mice on a high-protein diet for 2 months exhibit increased plasma Lcn2 (lipocalin-2) levels, a biomarker for renal dysfunction and oxidative stress
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• females fed a high-protein diet for 6 months develop severe multifocal tubulointerstitial nephritis, with a granular kidney cortex appearance, and fine microvesicular cytoplasmic changes in the convoluted proximal segment tubules
• however, glomeruli appear normal and podocyte foot processes are not effaced in mice fed a high-protein diet for 6 months
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• females fed a high-protein diet for 2 months exhibit higher methylmalonic acid concentrations in the brain compared to mice fed regular chow
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N |
• liver appears normal in mice fed a high-protein diet
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | DOID:0060740 |
OMIM:251000 |
J:200689 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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