Phenotypes associated with this allele

• Allele Symbol: Aspa^nur7
• Allele Name: neurological 7
• Allele ID: MGI:2671733
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Aspa^nur7/Aspa^nur7	involves: C57BL/6J	MGI:3027206
cx2	Aspa^nur7/Aspa^nur7 Nat8l^tm1.2Meck/Nat8l^tm1.2Meck	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:5771696
cx3	Aspa^nur7/Aspa^nur7 Nat8l^tm1.2Meck/Nat8l^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J	MGI:5771768
cx4	Aspa^nur7/Aspa^nur7 Ugt8a^tm1Pop/Ugt8a^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:3826778

Genotype
MGI:3027206

hm1

• 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 )

• 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

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

• myelin degeneration is more pronounced at P70 than at P21

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

Genotype
MGI:5771696

cx2

• Allelic Composition: Aspa^nur7/Aspa^nur7; Nat8l^tm1.2Meck/Nat8l^tm1.2Meck
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

mortality/aging

premature death ( J:226682 )

• reduced lifespan

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:226682 )

N • mice exhibit normal sphingolipid composition

abnormal enzyme/coenzyme level ( J:226682 )

• N-acetylaspartate levels in the brain are absent

behavior/neurological

behavior/neurological phenotype ( J:226682 )

N • mice exhibit normal rearing, normal total distance traveled, and normal latency to fall off the rotarod

growth/size/body

growth/size/body region phenotype ( J:226682 )

N • normal body weight

nervous system

nervous system phenotype ( J:226682 )

N • mice do not develop spongy degeneration or vacuolation in the brain and myelin structure appears normal with no demyelination

N • mice exhibit normal thickness of myelin sheaths relative to axon caliber, and do not exhibit axonal degeneration or astrogliosis

abnormal astrocyte morphology ( J:226682 )

• enlargement of pale astrocytic somata extending unusually broad processes that tend to group neighboring axons into microfascicles

Genotype
MGI:5771768

cx3

• Allelic Composition: Aspa^nur7/Aspa^nur7; Nat8l^tm1.2Meck/Nat8l⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J

behavior/neurological

decreased vertical activity ( J:226682 )

• rearing is reduced

decreased locomotor activity ( J:226682 )

• total distance traveled by mice is reduced

mortality/aging

mortality/aging ( J:226682 )

N • mice exhibit improved survival rate compared to single Aspa^nur7 homozygotes

growth/size/body

decreased body weight ( J:226682 )

• body weight is slightly reduced compared with controls but increased compared to single Aspa^nur7 homozygotes

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:226682 )

• N-acetylaspartate levels in the brain are reduced compared to single Aspa^nur7 homozygotes, but still increased compared to wild-type mice

nervous system

abnormal brain morphology ( J:226682 )

• N-acetylaspartate-derived neuropeptide NAAG levels are reduced by 22% in 1 year old brains

brain vacuoles ( J:226682 )

• vacuolation in the corpus callosum at P21 is less intense than in other white matter tracts

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

astrocytosis ( J:226682 )

• astrogliosis at P21 and P60

spongiform encephalopathy ( J:226682 )

• mice exhibit less spongy degeneration compared to single Aspa^nur7 homozygotes, most obvious in the pons and midbrain and also visible in the cerebellum and other brain regions

• spongy degeneration worsens with age

Genotype
MGI:3826778

cx4

• Allelic Composition: Aspa^nur7/Aspa^nur7; Ugt8a^tm1Pop/Ugt8a⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

nervous system

decreased oligodendrocyte number ( J:143201 )

• mice exhibit reduced numbers of oligodendrocytes compared to in wild-type mice

spongiform encephalopathy ( J:143201 )

• mice exhibit progressive neuropathy similar to in Aspa^nur7 homozygotes

abnormal myelination ( J:143201 )

• 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 70% compared to in wild-type mice

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

behavior/neurological

impaired coordination ( J:143201 )

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