Phenotypes Associated with This Genotype

Genotype
MGI:5708062

• Allelic Composition: L2hgdh^{Gt(DC0625)Wtsi}/L2hgdh^{Gt(DC0625)Wtsi}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

Spongiotic appearance of the L2hgdh^{Gt(DC0625)Wtsi}/L2hgdh^{Gt(DC0625)Wtsi} brain

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:228407 )

• mice show increased sensitivity to pentylenetetrazole induced convulsive seizures

abnormal habituation ( J:228407 )

• mice show decreased habituation to a known environment

impaired spatial learning ( J:228407 )

• in the Morris water maze, mutants show increased time of escape latency than controls and during the probe test on the fifth day when the platform is removed, mice spend less time in the quadrant where the platform had been present, indicating reduced learning capacity

abnormal spatial working memory ( J:228407 )

• in the Y maze, mice show a lower percentage of alternations, indicating impaired working memory

increased vertical activity ( J:228407 )

• rearing is increased about 2.6-fold

increased locomotor activity ( J:228407 )

• the distance moved when placed in a novel environment is increased by about 175%

fatigue ( J:228407 )

• mice appear to be more susceptible to fatigue in the wire test

• however, mice show normal muscle strength in the limbs

homeostasis/metabolism

abnormal amino acid level ( J:228407 )

• 3.4-fold increase in lysine, 2.3-fold increase in arginine, and 1.7-fold increase in free ethanolamine in the brain

• depletion of saccharopine and 45 and 22% decrease in glutamine and glutamate in the brain

• however, amino acid levels in the plasma and testis are normal

nervous system

increased susceptibility to pharmacologically induced seizures ( J:228407 )

• mice show increased sensitivity to pentylenetetrazole induced convulsive seizures

abnormal brain morphology ( J:228407 )

• 5-7 month old brain shows extensive spongiotic appearance, predominantly in the caudate putamen, the basal ganglia, and the brainstem, in particular in the pencils of Wilson and the white matter fascicles, where the myelin bundles are distorted

• deep layers of the cerebral cortex, the corpus callosum, and cerebellar nuclei have a spongiotic appearance

abnormal glial cell morphology ( J:228407 )

• many empty-looking dilated cell processes that contain altered, often dilated, organelles (vacuoles inside vacuoles) are seen in the glia

abnormal oligodendrocyte morphology ( J:228407 )

• cytoplasm of oligodendrocytes appears vacuolated; vacuoles do not contain lipids or mucin accumulation

abnormal myelin sheath morphology ( J:228407 )

• the myelin sheath of axons often appears disrupted, sometimes with spaces dissociating the myelin layers

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
L-2-hydroxyglutaric aciduria		DOID:0050574	OMIM:236792	J:228407