Phenotypes Associated with This Genotype

Genotype
MGI:3639891

• Allelic Composition: Sod2^tm1Cje/Sod2^tm1Cje
• Genetic Background: involves: C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:45913 )

• die between 3 and 13 days of age

• treatment with Manganese 5, 10 ,15, 20-tetrakis (4-benzoic acid) porpryrin (MnTBAP, a superoxide dismutase mimetic that does not cross the blood-brain barrier) increases survival time to a mean life span of 16.4 days compared to 8.3 days without treatment

cardiovascular system

dilated cardiomyopathy ( J:45913 )

• not detected in mice treated with MnTBAP

nervous system

abnormal brainstem morphology ( J:45913 )

• 9 of 16 mice older than 12 days of age display focal spongiform changes

• vacuoles are most commonly seen in the reticulotegmental nucleus of the pons, the superior and medioventral periolivary nuclei, and in regions of the motor nucleus of cranial nerves V and VII

abnormal cerebral cortex morphology ( J:45913 )

• mice older than 12 days of age display symmetric spongiform changes in large areas of the cerebral cortex, primarily in the mid to lower layers of the grey matter and the immediate subcortical white matter

• vacuoles are mostly present in the neuropil and occasionally in the neuronal perikaryon

abnormal cerebellum morphology ( J:45913 )

• 9 of 16 mice older than 12 days of age display focal spongiform changes

brain vacuoles ( J:45913 )

• no changes in brain morphology are seen in untreated mice before 10 days of age

• many of the vacuoles are surrounded by thin myelin lamellae

abnormal optic nerve morphology ( J:71457 )

• cross-sectional area is smaller; however, the ultrastructure appears normal in 20 to 21 day old MnTBAP treated mice

spongiform encephalopathy ( J:45913 )

• in MnTBAP treated mice

behavior/neurological

impaired righting response ( J:45913 )

• in MnTBAP treated mice

tremors ( J:45913 )

• in MnTBAP treated mice intermittent head tremors develop after P12

ataxia ( J:45913 )

• mice treated with MnTBAP develop progressive ataxia starting in the hindlimbs at about P12 and eventually spreading to the frontlimbs

• older mice display a wide-based gait, sway from side to side, and frequently fall with falls sometimes resulting in multiple rolls

abnormal gait ( J:45913 )

• at about P12 MnTBAP treated mice develop ataxia in the hindlimbs with alternating extensor dystonic-like posturing of the hindlimbs and pivoting on the extended limb

vision/eye

abnormal optic nerve morphology ( J:71457 )

• cross-sectional area is smaller; however, the ultrastructure appears normal in 20 to 21 day old MnTBAP treated mice

abnormal retina morphology ( J:71457 )

• in 20 to 21 day old MnTBAP treated mice total retinal thickness, peripheral retinal thickness, and thickness of the combined nerve fiber, ganglion cell, and inner plexiform layers are reduced

• unlike wild-type mice total retinal thickness does not increase between 9-10 and 20-21 days of age

abnormal retina pigment epithelium morphology ( J:71457 )

• abnormal mitochondria are more common at 16 and 20-21 days of age in MnTBAP treated mice compared to controls

• mitochondrial abnormalities include foci of swelling, matrix pallor, and disorganization of the cristae

thin retina inner nuclear layer ( J:71457 )

• thinner at 20-21 days of age in MnTBAP treated mice

abnormal retina photoreceptor layer morphology ( J:71457 )

• the central and overall photoreceptor layer are thinner at 9-10 and 20-21 days of age, respectively, in MnTBAP treated mice

liver/biliary system

hepatic steatosis ( J:45913 )

• lipid accumulation is decreased with MnTBAP treatment

growth/size/body

postnatal growth retardation ( J:45913 )

• weight gain is improved with MnTBAP treatment

muscle

dilated cardiomyopathy ( J:45913 )

• not detected in mice treated with MnTBAP

pigmentation

abnormal retina pigment epithelium morphology ( J:71457 )

• abnormal mitochondria are more common at 16 and 20-21 days of age in MnTBAP treated mice compared to controls

• mitochondrial abnormalities include foci of swelling, matrix pallor, and disorganization of the cristae

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:45913
Canavan disease		DOID:3613	OMIM:271900	J:45913
Leigh disease		DOID:3652	OMIM:256000	J:45913