Phenotypes associated with this allele

• Allele Symbol: Tg(Alb-Mut)#Cpv
• Allele Name: transgene insertion, Charles P Venditti
• Allele ID: MGI:5527452
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Mmut^tm1Cpv/Mmut^tm1Cpv Tg(Alb-Mut)#Cpv/0	involves: C57BL/6	MGI:5527455

Genotype
MGI:5527455

cx1

• Allelic Composition: Mmut^tm1Cpv/Mmut^tm1Cpv; Tg(Alb-Mut)#Cpv/0
• Genetic Background: involves: C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Enlarged mitochondria with whorl-like cristae in Mmut^tm1Cpv/Mmut^tm1Cpv Tg(Alb-Mut)#Cpv/0 mice fed a high-protein diet

mortality/aging

premature death ( J:200689 )

• 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

weight loss ( J:200689 )

♀ • 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

increased circulating creatinine level ( J:200689 )

♂ • males, but not females, fed a high-protein diet for 2 months exhibit an increase in serum creatinine

increased circulating methylmalonic acid level ( J:200689 )

• elevation in plasma methylmalonic acid levels

• females fed a high-protein diet exhibit increased plasma methylmalonic acid levels

decreased circulating bicarbonate level ( J:200689 )

♂ • males fed a regular diet exhibit lower plasma bicarbonate levels

increased circulating lipocalin 2 level ( J:200689 )

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

increased circulating chloride level ( J:200689 )

♂ • males fed a regular diet exhibit higher plasma chloride concentrations

metabolic acidosis ( J:200689 )

♂ • 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

tubulointerstitial nephritis ( J:200689 )

♀ • 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

abnormal kidney morphology ( J:200689 )

♀ • 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

abnormal renal tubule morphology ( J:200689 )

• multiple matrix granules/deposits in the renal tubular cytosol

decreased renal glomerular filtration rate ( J:200689 )

• 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

abnormal renal reabsorption ( J:200689 )

• 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

abnormal mitochondrial crista morphology ( J:200689 )

♀ • 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

abnormal mitochondrial matrix morphology ( J:200689 )

♀ • 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

oxidative stress ( J:200689 )

• 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

tubulointerstitial nephritis ( J:200689 )

♀ • 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

abnormal brain morphology ( J:200689 )

♀ • 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

liver/biliary system phenotype ( J:200689 )

♀N • liver appears normal in mice fed a high-protein diet

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