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Phenotypes Associated with This Genotype
Genotype
MGI:5527455
Allelic
Composition
Mmuttm1Cpv/Mmuttm1Cpv
Tg(Alb-Mut)#Cpv/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mmuttm1Cpv mutation (0 available); any Mmut mutation (2 available)
Tg(Alb-Mut)#Cpv mutation (0 available)
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

mortality/aging
• 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

growth/size/body
• 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

homeostasis/metabolism
• elevation in plasma methylmalonic acid levels
• females fed a high-protein diet exhibit increased plasma methylmalonic acid levels
• males, but not females, fed a high-protein diet for 2 months exhibit an increase in serum creatinine
• males fed a regular diet exhibit lower plasma bicarbonate levels
• males fed a regular diet exhibit higher plasma chloride concentrations
• 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

renal/urinary system
• 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
• 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
• multiple matrix granules/deposits in the renal tubular cytosol
• 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
• 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

cellular
• 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
• 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
• mice on a high-protein diet for 2 months exhibit increased plasma Lcn2 (lipocalin-2) levels, a biomarker for renal dysfunction and oxidative stress

immune system
• 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

nervous system
• females fed a high-protein diet for 2 months exhibit higher methylmalonic acid concentrations in the brain compared to mice fed regular chow

liver/biliary system
N
• liver appears normal in mice fed a high-protein diet


Contributing Projects:
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
03/24/2020
MGI 6.15
The Jackson Laboratory