Mouse Genome Informatics
hm
    Aldh5a1tm1Kmg/Aldh5a1tm1Kmg
involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• if untreated, homozygotes die of fatal seizures at day P16-P22
• therapeutic intervention with anticonvulsants phenobarbital or phenytoin fails to ameliorate survival
• in contrast, intervention with vigabatrin or the GABAB receptor antagonist CGP 35348 prevents tonic-clonic convulsions and prolongs survival
• administration of taurine, which is derived from the metabolism of cysteine and is highly present in mother's milk, via drinking water (up to 5,000 mg/kg/d) provides rescue through the critical period

behavior/neurological
• homozygotes display truncal ataxia at ~P15-P18
• at ~P15-P18, homozygotes display spasms and myoclonic seizures, leading to status epilepticus and death
• at about P15-P18, homozygotes display spasms and tonic seizures
• at P1-P16, unrestrained mutant neonates exhibit absence seizures identified by EEG analysis

growth/size/body
• homozygotes appear normal during the first days of life but display a 20-30% reduction in body weight relative to wild-type

homeostasis/metabolism
N
• in mutant brain, the concentrations of glutamic acid and succinic acid are comparable to those of wild-type (J:71949)
• homozygotes exhibit normal levels of Kreb's cycle intermediates in brain extracts, suggesting that global brain oxidative metabolism is unaffected (J:75773)
• homozygotes exhibit normal levels of total beta-alanine in urine and total homogenates of mutant brain, heart and pancreas, but elevated concentrations in kidney and liver homogenates (J:75773)
• homozygotes show a significant reduction of glutamine in mutant brain homogenates, despite normal glutamine synthetase protein and mRNA levels (J:75773)
• in brain, glutamine depletion is detected in the frontal cortex, parietal cortex, hippocampus and cerebellum (J:75773)
• notably, glutamine levels are normal in mutant liver and kidney extracts (J:75773)
• in brain extracts, P0-P18 homozygotes show high GABA/low glutamine both before, and after, the period of lethal tonic-clonic seizures (J:91856)
• brain homogenates show additional amino acid neurotransmitter abnormalities which may temporally correlate with the onset of lethal convulsions (J:91856)
• homozygotes contain elevated amounts of gamma-hydroxybutyric (GHB) and total 4-aminobutyric acid (GABA) in urine
• in mutant liver and brain homogenates, the amounts of GHB and total GABA are increased 30-45 and 2.5-3 fold, respectively, relative to wild-type (J:71949)
• in addition, homozygotes show elevated amounts of GHB and total GABA in homogenates of mutant kidney, pancreas and heart (J:75773)

muscle
• at ~P15-P18, homozygotes display spasms and myoclonic seizures, leading to status epilepticus and death

renal/urinary system
• homozygotes contain elevated amounts of gamma-hydroxybutyric (GHB) and total 4-aminobutyric acid (GABA) in urine

nervous system
• at ~P15-P18, homozygotes display spasms and myoclonic seizures, leading to status epilepticus and death
• at about P15-P18, homozygotes display spasms and tonic seizures
• at P1-P16, unrestrained mutant neonates exhibit absence seizures identified by EEG analysis
• in homozygotes, preliminary data indicated astrogliosis of the hippocampus
• at P1-P16, unrestrained mutant neonates exhibit absence seizures identified by EEG analysis

Mouse Models of Human Disease
OMIM IDRef(s)
Succinic Semialdehyde Dehydrogenase Deficiency; SSADHD 271980 J:91856