Phenotypes Associated with This Genotype

Genotype
MGI:6491217

• Allelic Composition: Aldh7a1^{tm1d(EUCOMM)Hmgu}/Aldh7a1^{tm1d(EUCOMM)Hmgu}
• Genetic Background: B6(FVB)-Aldh7a1^{tm1d(EUCOMM)Hmgu}

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:298561 )

• lower than the expected frequency of mice is seen at weaning

homeostasis/metabolism

abnormal amino acid level ( J:298561 )

• serine, proline, alanine, citrulline, leucine, alanine, tyrosine, phenylalanine, ornithine, tryptophan and histidine levels are elevated in the liver of adult mice

decreased glycine level ( J:298561 )

• glycine levels are lower in the brain

increased leucine level ( J:298561 )

• leucine levels are elevated in the liver of adult mice

decreased lysine level ( J:298561 )

• lysine levels are lower in the brain

increased ornithine level ( J:298561 )

• ornithine levels are elevated in the brain and the liver

increased phenylalanine level ( J:298561 )

• phenylalanine levels are elevated in the liver of adult mice

increased proline level ( J:298561 )

• proline levels are elevated in the liver of adult mice

increased serine level ( J:298561 )

• serine levels are elevated in the liver of adult mice

increased circulating noradrenaline level ( J:298561 )

• norepinephrine levels and its metabolite, normetanephrine, are increased in the plasma

• however, no differences in the levels of the neurotransmitters gamma-aminobutyric acid (GABA) and glutamic acid are seen

abnormal vitamin level ( J:298561 )

• mice consuming a high lysine/low pyridoxine diet exhibit lower levels of phosphorylated form of pyridoxal (PLP), a vitamin B6 vitamer, in the brain and the liver

• mice fed the high lysine/pyridoxine diet treated with pyridoxine exhibit restoration of PLP levels in the brain and the liver to almost normal levels

• however, mice fed a normal diet show no difference in the concentration of vitamin B6 vitamers in the plasma, brain or liver

abnormal amino acid metabolism ( J:298561 )

• mice accumulate high concentrations of upstream lysine metabolites in the brain and liver, indicating dysregulation of lysine metabolites

• upstream lysine catabolite products delta¹-piperideine-6-carboxylic acid (P6C), pipecolic acid (PIP), saccharopine (SAC), and alpha-aminoadipic semialdehyde (alpha-AAA) are increased in the brain tissue at P0

• -lysine catabolite PIP is elevated in liver tissue at P0

• lysine catabolic products P6C, alpha-AASA, and PIP accumulate in higher concentrations in the brain and liver tissues of adults

• P6C accumulates to higher levels in brain tissue of adults than in neonates

• PIP accumulates to higher levels in brain tissue of neonates than in adults

• P6C levels are nominally higher in liver tissue than in brain tissue of adults

• PIP levels are higher in brain tissue than in liver tissue in both neonates and adults

behavior/neurological

behavior/neurological phenotype ( J:298561 )

N • mice show normal locomotor activity in the open field, no anxiety-like behavior in the open field, elevated plus maze and novel object recognition, no depressive-like behavior in the forced swim test, normal spatial memory and learning in the Morris water maze, and normal coordination and motor learning on the accelerating rotarod

seizures ( J:298561 )

• mice fed a high lysine (4.7%) and low (1.6 ppm) pyridoxine diet develop seizures as early as 23.5 hours post-diet administration and die or are euthanized to due severity mice treated with pyridoxine and fed the high lysine and low pyridoxine diet do not exhibit seizures, indicating that mice develop pyridoxine-dependent seizures due to the depletion of PLP

• however, mice fed a normal diet (low lysine/high pyridoxine) show no evidence of epileptic seizures on a normal diet

cellular

oxidative stress ( J:298561 )

• methionine sulfoxide levels are elevated in the brain, indicating oxidative stress

nervous system

seizures ( J:298561 )

• mice fed a high lysine (4.7%) and low (1.6 ppm) pyridoxine diet develop seizures as early as 23.5 hours post-diet administration and die or are euthanized to due severity mice treated with pyridoxine and fed the high lysine and low pyridoxine diet do not exhibit seizures, indicating that mice develop pyridoxine-dependent seizures due to the depletion of PLP

• however, mice fed a normal diet (low lysine/high pyridoxine) show no evidence of epileptic seizures on a normal diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pyridoxine-dependent epilepsy		DOID:0080768		J:298561