Phenotypes Associated with This Genotype

Genotype
MGI:3027206

• Allelic Composition: Aspa^nur7/Aspa^nur7
• Genetic Background: involves: C57BL/6J

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

nervous system

seizures ( J:143201 , J:226682 )

• as mice age (J:143201)

abnormal brain morphology ( J:226682 )

• N-acetylaspartate-derived neuropeptide NAAG levels are reduced by 25% in 1 year old brains

enlarged lateral ventricles ( J:143201 )

• widened at P70

abnormal brain white matter morphology ( J:226682 )

• white matter degeneration in the cerebellum, corpus callosum, and other brain regions

brain vacuoles ( J:143201 , J:226682 )

• at P14, vacuoles are detected in the cerebellar white matter in the Purkinje cell layer and brainstem unlike in wild-type mice (J:143201)

• mice exhibit progressive vacuolar degeneration that affects the forebrain, cerebral cortex, hippocampus, subcortical white matter regions, midbrain, pons and cerebellum where the granule cell layer, Purkinje cell layer and white matter show defects unlike in wild-type mice (J:143201)

• lateral sections of the cerebellar sagittal plane exhibit more increasingly severe white matter lesions (J:143201)

• at P70, vacuolization expands into subcortical white matter, brainstem, cerebellum and spinal cord gray matter (J:143201)

• at P70, the dorsal pons is more severely affected than the rest of the pons by vacuolization (J:143201)

• vacuolization is caused by the splitting of the myelin sheath (J:143201)

• vacuoles are seen as swollen axons surrounded by compressed myelin layers (J:226682)

• vacuolation in the corpus callosum at P21 is less intense than in other white matter tracts (J:226682)

• vacuolation in the corpus callosum is less severe at P60 compared with P21 and almost undetectable in 1 year old mice (J:226682)

astrocytosis ( J:143201 , J:226682 )

abnormal oligodendrocyte morphology ( J:143201 )

• at P21, loss of oligodendrocytes occurs in lesion areas unlike in wild-type mice

• at P30, oligodendrocyte loss occurs in the spinal cord gray matter unlike in wild-type mice

• at P70, the number of oligodendrocytes is increased in the brainstem (medial pons) and spinal cord gray matter

axon degeneration ( J:143201 , J:226682 )

• at P120, 30% fewer axons are found in the cerebellar white matter compared to in heterozygous mice (J:143201)

spongiform encephalopathy ( J:143201 , J:226682 )

• beginning at P14, mice exhibit progressive spongiform degeneration (J:143201)

• mice exhibit progressive neuropathy similar to in Aspa^nur7/Aspa^nur7 Ugt8a^tm1Pop/Ugt8a⁺ mice (J:143201)

• massive spongy degeneration of white matter in the cerebellum, most pronounced around the deep cerebellar nuclei and less prominent within the folial white matter (J:226682)

• within the corpus callosum, white matter degeneration mainly affects the immediate subcortical callosal surface (J:226682)

• spongy degeneration worsens with age (J:226682)

abnormal myelination ( J:143201 )

• however, the level of hydroxyl fatty acid-containing Galc cerebroside is normal

• myelin degeneration is more pronounced at P70 than at P21

• at P21, myelin sheath thickness is reduced compared to in wild-type mice

• at P21, mice exhibit a 40% decrease in phosphatidyl ethanolamine in myelin compared to in wild-type mice

• at P21, normal fatty acid-containing Galc cerebroside is reduced 40% compared to in wild-type mice

demyelination ( J:226682 )

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:226682 )

• N-acetylaspartate levels are increased in the brain

abnormal sphingolipid level ( J:226682 )

• mice exhibit abnormal sphingolipid composition, showing a reduction in the concentration of nonhydroxylated fatty acid containing GalC (NFA-GalC) in the brain at P21 and P60, whereas 2-hydroxylated fatty acid-containing GalC (HFA-GalC) levels are reduced to a lesser extent at P60

behavior/neurological

lethargy ( J:85113 )

tremors ( J:85113 , J:143201 , J:226682 )

• late onset; develop upon movement (J:85113)

• adult mice tremble during movement (J:143201)

• mice develop more severe tremors as they age (J:143201)

• at P70, tremors are slightly increased compared to in younger mice (J:143201)

ataxia ( J:143201 , J:226682 )

• at P21, mice exhibit a wide ataxic gait (J:143201)

• at P70, ataxia is slightly increased compared to in younger mice (J:143201)

impaired coordination ( J:143201 , J:226682 )

• at P42 to P56, mice exhibit a 50% decreased in latency to fall on a rotarod compared to wild-type mice (J:143201)

• latency to fall off the rotating rod is reduced by about 50% (J:226682)

abnormal gait ( J:143201 )

• at P21, mice exhibit a wide ataxic gait

decreased vertical activity ( J:226682 )

decreased locomotor activity ( J:85113 , J:143201 , J:226682 )

• animals have reduced open field activity (J:85113)

• young mice are hypoactive (J:143201)

• total distance traveled by mice is reduced (J:226682)

seizures ( J:143201 , J:226682 )

• as mice age (J:143201)

mortality/aging

premature death ( J:226682 )

• majority of mice die within 4 weeks

growth/size/body

decreased body size ( J:85113 , J:143201 )

• affected animals are smaller than littermates (J:85113)

decreased body weight ( J:226682 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Canavan disease		DOID:3613	OMIM:271900	J:143201 , J:226682