Analysis Tools|
Allele Symbol Allele Name Allele ID |
Opa1+ wild type MGI:2440943 |
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| Summary |
5 genotypes
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Data Sources
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• loss of retinal ganglion cell axons at 16 months of age
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• the number of retinal ganglion cell somas is decreased, reaching a 40% and 50% reduction at 9 and 16 months of age, respectively
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• optic nerves exhibit axonal alterations, which include general autophagy with typical lamellar bodies composed of double membrane structures corresponding to fused lysosomes and phagosomes
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• visual evoked potential shows a progressive increase in latencies and a non-significant reduction in amplitudes, reaching 12% and 20% increase in the N- and P-wave, respectively, at 13 months, indicating progressive visual failure
• however, electroretinogram profiles are not altered
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• mice develop progressive visual failure
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• mice do not show differences in auditory function at 3 months of age showing an mean auditory brainstem response thresholds of about 27 dB sound pressure level, but by 5 months of age, mice show a significant 30 dB auditory brainstem response threshold elevation at the highest frequency of 32 kHz and by 11 months of age, mice are severely deaf with a mean auditory brain stem response threshold of 59 dB sound pressure level
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• in the CatWalk test, mice show a decrease in the front and hind paws print area, with hind paws more severely affected showing a 40% reduction for the left paw
• females show a reduced footprint maximum intensity, especially on the left ipsilateral side, while males show an increase in the maximum intensity of the front paws, suggesting that males and females compensate differently in their hind paw locomotion
• male mice show an increase in the duration of the front paws stance phase, spending more time on the front paw, while females show a general decrease of the stance phase affecting more the left hind paw
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• mice show normal behavior before 5 months of age, but at 5 and 11 months, mice show increasing difficulties in remaining on the rotating bar and fall down more rapidly than controls
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• 5 month old cardiac muscles show aberrant structural conformation of myofibrils with large punctuated mitochondria
• 23% fewer mitochondria in cardiac muscle at 5 months of age
• 12% larger mitochondria in cardiac muscle at 5 months of age
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• at 5 months of age
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• glycolytic fibers exhibit mitochondrial degeneration characterized by lysosome-like structures localized inside the vacuolated matrix
• neuronal tissues show a mild increase in mitochondrial DNA content which becomes significant in the optic nerve
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• muscles have a mild decrease in mitochondrial DNA amounts, while heart shows a 54% decrease
• however, no mitochondrial DNA deletions are seen in glycolytic muscle, retina and heart
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• in glycolytic fibers, mitochondria show loss of cristae organization
• in oxidative fibers, subsarcolemmal mitochondrial aggregates are seen with densely packed cristae, combined with some lipid droplets
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• in glycolytic fibers, mitochondria have a swollen and vacuolated shape, with loss of cristae organization
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• 23% fewer mitochondria in cardiac muscle at 5 months of age
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• glycolytic and oxidative muscle fibers of 5 month old mice show an increase in the number of mitochondria
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• glycolytic and oxidative muscle fibers of 5 month old mice show an increase in size of mitochondria
• 12% larger mitochondria in cardiac muscle at 5 months of age
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• glycolytic and oxidative muscle fibers show increased mitochondria in phagolysosomes undergoing mitophagy and general autophagy
• 6-fold increase in autophagic structures (autophagy, mitophagy, and vacuolated mitochondria) in 5 month old glycolytic fibers which are still present at 16 months, whereas oxidative fibers show only a slight increase of these structures with age
• nerves from central and peripheral systems show autophagic axonal degenerations preceding myelin alterations in young mice
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• mice exhibit an increase in mitophagy, with mitochondria seen inside phagolysosomes in both glycolytic and oxidative muscle fibers
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• mitochondrial dysfunction in the retina, optic nerve, and glycolytic muscle
• at 5 months of age, a 46% decrease in complex IV cytochrome oxidase activity is seen in the retina
• at 11 months of age, a 21% and 20% decrease in complex IV cytochrome oxidase activity is seen in the optic nerve and in glycolytic muscle, respectively
• 44% reduction in the cytochrome oxidase maximal respiration rate in glycolytic muscle is seen before the reduced cytochrome oxidase enzymatic activity
• however, mitochondrial enzymatic activity and cytochrome oxidase functionality are not altered in oxidative muscles (soleus, heart) and the brain
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• glycolytic and oxidative muscle fibers show increased mitochondria in phagolysosomes undergoing mitophagy and general autophagy
• 6-fold increase in autophagic structures (autophagy, mitophagy, and vacuolated mitochondria) in 5 month old glycolytic fibers which are still present at 16 months, whereas oxidative fibers show only a slight increase of these structures with age
• nerves from central and peripheral systems show autophagic axonal degenerations preceding myelin alterations in young mice
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• mice exhibit an increase in mitophagy, with mitochondria seen inside phagolysosomes in both glycolytic and oxidative muscle fibers
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• increase in total creatine levels in the cerebellum
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• at 5 months of age, a 46% decrease in complex IV cytochrome oxidase activity is seen in the retina
• at 11 months of age, a 21% and 20% decrease in complex IV cytochrome oxidase activity is seen in the optic nerve and in glycolytic muscle, respectively
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• 5 month old cardiac muscles show aberrant structural conformation of myofibrils with large punctuated mitochondria
• 23% fewer mitochondria in cardiac muscle at 5 months of age
• 12% larger mitochondria in cardiac muscle at 5 months of age
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• 5 month old mice show alterations of the muscle ultrastructure in both glycolytic and oxidative fibers, with an increase in the number and size of mitochondria
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• muscles have a mild decrease in mitochondrial DNA amounts, while heart shows a 54% decrease
• however, no mitochondrial DNA deletions are seen in glycolytic muscle, retina and heart
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• loss of myofibrils in cardiac muscle that gives rise to sarcomere disorganization, with large zones of autophagic and mitophagic materials
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• 4 of 8 mice at 11 months of age exhibit dilatation of the fourth ventricle, with 2 of 8 mice showing dilatation of both the lateral and fourth ventricles
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• lateral ventricle area is increased
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• 5 of 8 mice at 11 months of age exhibit lateral ventricle dilatation, with 2 of 8 mice showing dilatation of both the lateral and fourth ventricles
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• cerebellum maximal length is decreased
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• 7 of 8 mice exhibit cerebral and/or cerebellar atrophies
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• loss of retinal ganglion cell axons at 16 months of age
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• the number of retinal ganglion cell somas is decreased, reaching a 40% and 50% reduction at 9 and 16 months of age, respectively
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• optic nerves exhibit axonal alterations, which include general autophagy with typical lamellar bodies composed of double membrane structures corresponding to fused lysosomes and phagosomes
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• sciatic nerve degeneration is seen starting at 5 months, characterized by presence of hyper dense autophagic axons and myelin degeneration that increases with age
• at 16 months of age, a 30% loss of axons is seen in sciatic nerves, with remaining exons showing a 10% increase of their G-ratio
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• at 5 months of age, optic nerves show a premature increase in axonal degenerations which are highly significant by 16 months of age
• at 16 months of age, a 30% loss of axons is seen in sciatic nerves
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• 16 month old mice exhibit demyelination, with a 6% decrease in myelin thickness
• myelin degeneration leads to myelin sheath vacuolization, followed by complete disintegration of myelin layers and axons
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| optic atrophy | DOID:5723 |
OMIM:PS165500 |
J:237963 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 52% of mice
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• 33% of mice exhibit resting tremor of the upper limb unlike wild-type mice
• tremors are more prominent in males
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• some mice do not perform as well on a rotarod as wild-type mice
• overall, mice spend less time running on a rotarod compared with wild-type mice
• mice that exhibit tremors also perform worse on a rotarod compared with wild-type mice
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• under regular housing conditions
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| N |
• mice exhibit normal skeletal muscle morphology and muscle mitochondria DNA
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 13 months, fewer nuclei are found in the retinal ganglion cell layer compared to in wild-type mice
• at 17 months, one mouse exhibits loss of cells in the retinal ganglion cell layer to 20% to 40% compared with wild-type mice
• however, at 23 months the number of cells in the retinal ganglion layer is normal
• loss of ganglion cell layer cells is age related and begins at 2 months of age
• cell loss at 9 months is primarily in the mid-periphery to periphery of the retina
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• at 8 months, optic nerves exhibit loss of large and small axons, disorganized structure, axonal swelling, irregular myelination, distorted axon shapes, increased collageneous material, decreased neurofibrils, and abnormal mitochondria with disorganized cristae unlike in wild-type mice
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• mice exhibit gliosis of the optic nerve head unlike wild-type mice
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• at 13 months, fewer nuclei are found in the retinal ganglion cell layer compared to in wild-type mice
• at 17 months, one mouse exhibits loss of cells in the retinal ganglion cell layer to 20% to 40% compared with wild-type mice
• however, at 23 months the number of cells in the retinal ganglion layer is normal
• loss of ganglion cell layer cells is age related and begins at 2 months of age
• cell loss at 9 months is primarily in the mid-periphery to periphery of the retina
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• at 8 months, optic nerves exhibit loss of large and small axons, disorganized structure, axonal swelling, irregular myelination, distorted axon shapes, increased collageneous material, decreased neurofibrils, and abnormal mitochondria with disorganized cristae unlike in wild-type mice
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• mice exhibit gliosis of the optic nerve head unlike wild-type mice
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| N |
• mice exhibit normal hearing
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| optic atrophy | DOID:5723 |
OMIM:PS165500 |
J:154966 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are fertile
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• at 18 months, the optic nerve has defects in myelin bundles and optic nerve fascicles appearing as gross whirls of myelin along the nerve
• however, mice have normal optic nerves and retinas at 6 months of age
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• 11-13 month old mutants exhibit deficits in light-adapted visual responses; although the positive peak of the b-wave is similar to wild-type, the amplitude of the photopic negative response (immediately following negative deflection) is reduced at the two brightest intensities tested
• however, 11-13 month old mutants exhibit normal dark-adapted visual responses
• both rod and cone visual pathways remain in tact, however the differences in late evolving components of the light-adapted ERG and flash VEP responses that are seen indicate ganglion cell dysfunction
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• 11-13 month old mutants exhibit deficits in light-adapted flash visually evoked potentials (VEPs), showing a normal negative N1 component but a reduction in the subsequent positive deflection (P2 wave) at the brightest intensity tested
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• at 6 and 12 months, mice are not functionally totally blind
• at 12 months, mice track less well on all three gratings indicating a decrease in visual acuity
• at 12 months, mice exhibit increased nocturnal running when exposed to a light unlike wild-type mice indicating a reduction in vision
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• at 6 months, when transferred into an arena mice exhibit transfer arousal, freezing in place for a longer period of time than controls, decreased locomotor activity and increased provoked biting response
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• most mice display cells that have punctuated and completely dispersed mitochondria throughout the cytosol and nucleus, thereby giving cells a 'powdered' appearance
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• some embryos exhibit forebrain truncation
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• at 18 months, the optic nerve has defects in myelin bundles and optic nerve fascicles appearing as gross whirls of myelin along the nerve
• however, mice have normal optic nerves and retinas at 6 months of age
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• some embryos
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• some embryos
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| optic atrophy | DOID:5723 |
OMIM:PS165500 |
J:121779 , J:189276 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 01/28/2026 MGI 6.24 |
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