Phenotypes Associated with This Genotype

Genotype
MGI:3026845

• Allelic Composition: Mmut^tm1Pai/Mmut^tm1Pai
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:87081 )

• although homozygotes are born normally and exhibit normal activity and suckling shortly after birth, none of them survive past 24 hrs of age

behavior/neurological

absent gastric milk in neonates ( J:87081 )

• homozygotes display reduced/absent milk spots by 15-18 hrs of age

• however, large gastric milk spots are observed shortly after birth

abnormal suckling behavior ( J:87081 )

• homozygotes stop suckling by 15-18 hrs of age

decreased locomotor activity ( J:87081 )

• although homozygotes are initially vigorous, they show a gradual decrease in activity by 15-18 hrs of age

homeostasis/metabolism

increased circulating carnitine level ( J:87081 )

• newborn homozygotes show a ~6-fold increase in mean circulating propionylcarnitine (C3) levels relative to wild-type and heterozygous controls

• ratios of propionylcarnitine to free carnitine (C3:C0) and to acetylcarnitine (C3:C2) are ~7-fold higher than in controls

• blood levels of free carnitine (CO) and acetylcarnitine (C2) remain normal

methylmalonic aciduria ( J:87081 )

• urinary levels of methylmalonic and methylcitric acids are grossly increased, as shown by gas chromatography-mass spectrometry

• urinary levels of methylmalonic acid are grossly elevated shortly after birth, with progressive accumulation at various time points prior to death

• however, no evidence of ketonuria is observed

renal/urinary system

methylmalonic aciduria ( J:87081 )

• urinary levels of methylmalonic and methylcitric acids are grossly increased, as shown by gas chromatography-mass spectrometry

• urinary levels of methylmalonic acid are grossly elevated shortly after birth, with progressive accumulation at various time points prior to death

• however, no evidence of ketonuria is observed

respiratory system

respiratory distress ( J:87081 )

• homozygotes exhibit intermittent gasping prior to death

liver/biliary system

abnormal liver parenchyma morphology ( J:87081 )

• at 20 hrs (but not at 12 hrs) of age, homozygotes display a moderate fatty change in liver parenchyma

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:87081