Phenotypes Associated with This Genotype

Genotype
MGI:3038607

• Allelic Composition: Aspa^tm1Mata/Aspa^tm1Mata
• Genetic Background: involves: 129S5/SvEvBrd

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

mortality/aging

premature death ( J:89100 )

• of those that survive post weaning, life spans range from 1.5 to 9 months

preweaning lethality, incomplete penetrance ( J:89100 )

• 50% of homozygotes (4/8) die before weaning

homeostasis/metabolism

increased aspartic acid level ( J:89099 )

• the aspartate level in the brain is significantly higher compared to wild-types

decreased gamma-aminobutyric acid level ( J:89099 )

• the GABA level is 50% lower in the brain compared to wild-types

decreased glutamic acid level ( J:89099 )

• the level of glutamate in the brain is abnormally low compared to wild-types

adipose tissue

decreased total body fat amount ( J:89099 )

• by 6 months of age mutants have lower body fat compared to wild-types

behavior/neurological

lethargy ( J:89100 )

tremors ( J:89100 )

ataxia ( J:89100 )

• mutants are able to sustain their balance on the rotorod for only very short periodsmof time

abnormal gait ( J:89100 )

• mutants walk with splayed legs

• the pace of mutants is slower and shaky compared to wild-types

abnormal pain threshold ( J:89100 )

• homozygotes are insensitive to pain when their tails are cut for genotyping

growth/size/body

decreased body weight ( J:89099 , J:89100 )

• homozygotes are the same size as controls for the first 2 weeks after birth but by 4 weeks the body weight of mutants is significantly less than that of wild-types (J:89099)

• at 6 months the lean body mass of mutants is significantly less than that of wild-types (J:89099)

• at weaning homozygotes weigh significantly less than wild-types (J:89100)

megacephaly ( J:89099 , J:89100 )

• head circumference is significantly higher in mutants compared to wild-types (J:89099)

• macrocephaly with bulging of the fronto-nasal junction is seen in mutants (J:89100)

decreased body length ( J:89099 )

• crown-rump length is slightly lower in mutants compared to wild-types

skeleton

decreased bone mineral content ( J:89099 )

• whole body bone mineral content is slightly lower in mutant mice compared to wild-type at 6 months

• lumbar bone mineral content significantly decreases between 1 and 6 months in mutant mice

decreased bone mineral density ( J:89099 )

• whole body bone mineral density does not increase between 1 month and 6 months resulting in significantly lower whole body bone mineral density in mutant mice compared to wild-type at 6 months

decreased bone mineral density of lumbar vertebrae ( J:89099 )

• lumbar bone mineral density is significantly lower in mutant mice compared to wild-type

vision/eye

abnormal retina ganglion layer morphology ( J:89100 )

• vacuolation is seen in the ganglion layer of the retina

abnormal retina nerve fiber layer morphology ( J:89100 )

• vacuolation is seen in the nerve fiber layer of the retina

nervous system

abnormal brainstem morphology ( J:89100 )

• MRI signal intensity is abnormally high indicating higher than normal water content

abnormal diencephalon morphology ( J:89100 )

• MRI signal intensity is abnormally high indicating higher than normal water content

spongiform encephalopathy ( J:89100 )

• extensive vacuolation of the white matter of the deep cortex and white matter bundles of the corpus striatum is seen

• vacuolation is seen in the pyramidal area of the hippocampu

• degeneration is also seen in the cerebellum with the most severe changes seen in the Purkinje cell layer and less severe changes in the other layers

abnormal synaptic neurotransmitter level ( J:89099 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Canavan disease		DOID:3613	OMIM:271900	J:89099 , J:89100