Phenotypes associated with this allele

• Allele Symbol: Mmut^tm1.1Mrb
• Allele Name: targeted mutation 1.1, Matthias R Baumgartner
• Allele ID: MGI:6157363
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mmut^tm1.1Mrb/Mmut^tm1.1Mrb	involves: C57BL/6	MGI:6157364
ht2	Mmut^tm1Pai/Mmut^tm1.1Mrb	involves: 129S1/Sv * C57BL/6	MGI:6157365

Genotype
MGI:6157364

hm1

• Allelic Composition: Mmut^tm1.1Mrb/Mmut^tm1.1Mrb
• Genetic Background: involves: C57BL/6

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

growth/size/body

weight loss ( J:237040 )

• mice fed a high protein (HP) diet or a precursor-enriched (PE) diet comprised of increased levels of precursor amino acids of propionate pathway metabolites exhibit a rapid weight loss, with more pronounced weight loss of the PE diet

• mice fed a high protein diet and treated with cobalamin do no show weight loss

postnatal growth retardation ( J:237040 )

• mice show significant growth retardation after the age of about 100 days in females and about 150 days in males

homeostasis/metabolism

increased circulating carnitine level ( J:237040 )

• propionylcarnitine (normalized to acetylcarnitine) in blood is elevated, although to a lower extent than in compound heterozygous Mut^tm1Pai/Mut^tm1.1Mrb mice

• mice fed a HP or PE diet show further elevations in propionylcarnitine levels

• mice fed a HP diet and treated with cobalamin show delayed elevations in propionylcarnitine

increased circulating glycine level ( J:237040 )

• mice exhibit elevated glycine levels in blood

• however, other amino acid levels are mostly unchanged

increased circulating ammonia level ( J:237040 )

• mice fed a HP or PE diet show increased ammonia levels, indicative of metabolic crisis induction

• however, mice fed a regular chow diet exhibit normal ammonia levels

• mice fed a HP diet and treated with cobalamin exhibit delayed elevation of ammonia

abnormal fatty acids level ( J:237040 )

• mice exhibit increased levels of odd chain fatty acids in plasma, predominantly of the 13-carbon chain length fatty acid

• however, levels of even chain fatty acids are normal

acidosis ( J:237040 )

• methylmalonic acid is elevated in tissues and dried blood, although to a lower extent than in compound heterozygous Mut^tm1Pai/Mut^tm1.1Mrb mice

• mice fed a HP or PE diet show further elevations in methylmalonic acid levels

methylmalonic aciduria ( J:237040 )

• methylmalonic acid levels are elevated in urine, although to a lower extent than in compound heterozygous Mut^tm1Pai/Mut^tm1.1Mrb mice

• mice fed a HP or PE diet show further elevations in methylmalonic acid levels

renal/urinary system

methylmalonic aciduria ( J:237040 )

• methylmalonic acid levels are elevated in urine, although to a lower extent than in compound heterozygous Mut^tm1Pai/Mut^tm1.1Mrb mice

• mice fed a HP or PE diet show further elevations in methylmalonic acid levels

mortality/aging

mortality/aging ( J:237040 )

N • mice exhibit a normal life span

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:237040

Genotype
MGI:6157365

ht2

• Allelic Composition: Mmut^tm1Pai/Mmut^tm1.1Mrb
• Genetic Background: involves: 129S1/Sv * C57BL/6

growth/size/body

decreased body weight ( J:237040 )

• females show a 30% difference in body weight from wild-type mice at about 1 year of age

• however, food intake remains constant

weight loss ( J:237040 )

• mice fed a high protein (HP) diet or a precursor-enriched (PE) diet comprised of increased levels of precursor amino acids of propionate pathway metabolites exhibit a rapid weight loss, with more pronounced weight loss on the PE diet

• mice fed a high protein diet and treated with cobalamin show a slight protective effect, with a delay in weight loss, although increases in metabolite levels still occur

postnatal growth retardation ( J:237040 )

• mice show significant growth retardation after the age of about 100 days in females and about 150 days in males

homeostasis/metabolism

increased circulating carnitine level ( J:237040 )

• propionylcarnitine (normalized to acetylcarnitine) in blood is constantly elevated

• mice fed a HP or PE diet show further elevations in propionylcarnitine levels

increased circulating glycine level ( J:237040 )

• mice exhibit elevated glycine levels in blood

• however, other amino acid levels are mostly unchanged

increased circulating ammonia level ( J:237040 )

• mice fed a HP or PE diet show increased ammonia levels, indicative of metabolic crisis induction

• however, mice fed a regular chow diet exhibit normal ammonia levels

increased blood urea nitrogen level ( J:237040 )

• increase in plasma urea

increased urine chloride ion level ( J:237040 )

increased urine potassium level ( J:237040 )

increased urine sodium level ( J:237040 )

abnormal fatty acids level ( J:237040 )

• mice exhibit increased levels of odd chain fatty acids in plasma, including the 17-carbon chain length fatty acid

• however, levels of even chain fatty acids are normal

abnormal sphingolipid level ( J:237040 )

• mice exhibit an elevation of odd chain length sphingoid bases in plasma and tissues

• however, levels of even chain sphingoid bases remains normal

acidosis ( J:237040 )

• methylmalonic acid levels are elevated in tissues and dried blood

• however, mice show normal ammonia levels

• mice fed a HP or PE diet show further elevations in methylmalonic acid levels

increased lipocalin 2 level ( J:237040 )

• mice show an up-regulation in Lcn2 (lipocalin-2) at the mRNA and protein level in brain tissue, as well as increased protein levels of lipocalin-2 in kidney tissue

increased urine calcium level ( J:237040 )

increased urine magnesium level ( J:237040 )

methylmalonic aciduria ( J:237040 )

• methylmalonic acid levels in urine are constantly elevated

• mice fed a HP or PE diet show further elevations in methylmalonic acid levels

nervous system

abnormal brain morphology ( J:237040 )

• mice show increased levels of the biomarker lipocalin-2 in the brain

increased brain weight ( J:237040 )

• increase in brain weight at 1 month and 1 year of age

• however, brain histology is normal in the basal ganglia

• mice fed a HP or PE diet show increased brain weight (normalized to body weight)

• mice fed a high protein diet and treated with cobalamin show a slight protective effect, with no increase in brain weight, although increases in metabolite levels still occur

renal/urinary system

increased urine chloride ion level ( J:237040 )

increased urine potassium level ( J:237040 )

increased urine sodium level ( J:237040 )

increased urine calcium level ( J:237040 )

increased urine magnesium level ( J:237040 )

methylmalonic aciduria ( J:237040 )

• methylmalonic acid levels in urine are constantly elevated

• mice fed a HP or PE diet show further elevations in methylmalonic acid levels

abnormal kidney morphology ( J:237040 )

• mice show increased levels of the biomarker lipocalin-2 in kidney tissue indicating kidney damage

abnormal kidney physiology ( J:237040 )

• mice exhibit disturbed excretion of several electrolytes in urine, indicating renal tubular dysfunction

oliguria ( J:237040 )

• mice produce less urine during adulthood than controls, when normalized for body weight

• however, water intake is not different from controls

mortality/aging

mortality/aging ( J:237040 )

N • mice exhibit a normal life span

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:237040