Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1ftm1.1Sdie mutation
(1 available);
any
Cacna1f mutation
(19 available)
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vision/eye
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• progressive photoreceptor loss, with rod and cone photoreceptors affected to a similar degree
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• moderate reduction in outer nuclear layer (ONL) thickness at 2 and 8 months of age
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• increase in the percentage of apoptotic cells in the ONL at P28, however at 2 and 8 months of age, the percentage of apoptotic cells in the retina decreases to wild-type levels, indicating an initial peak of photoreceptor degeneration followed by a steady but moderate degeneration from two months onward
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• calcium responses to depolarization of photoreceptor terminals are undetectable
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• increase in the percentage of apoptotic cells in the ONL at P28, however at 2 and 8 months of age, the percentage of apoptotic cells in the retina decreases to wild-type levels
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• at photopic conditions, flash ERGs are not recordable in mutants
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• at scotopic conditions, ERGs display a residual a-wave
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• at scotopic conditions, a-wave amplitude is smaller at 2 and 8 months of age
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• b-wave in the EEG is absent
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nervous system
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• progressive photoreceptor loss, with rod and cone photoreceptors affected to a similar degree
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• photoreceptor ribbon synapses are abnormal
• cone photoreceptor terminals are either absent or not identifiable as such
• postsynaptic elements and synaptic ribbons are either absent of spherically shaped and free-floating at 2-8 months of age
• the rarely observed anchored rod photoreceptor ribbons are small and club-shaped
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• mice exhibit enhanced spouting of rod bipolar- and horizontal cell processes into the ONL already at P14 which peaks at P28 and then declines
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cellular
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• increase in the percentage of apoptotic cells in the ONL at P28, however at 2 and 8 months of age, the percentage of apoptotic cells in the retina decreases to wild-type levels
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1ftm1.1Sdie mutation
(1 available);
any
Cacna1f mutation
(19 available)
|
|
|
vision/eye
|
|
• irregular outgrowth of bipolar cell neurites
|
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• irregular outgrowth of horizontal cell neurites into the outer nuclear layer
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• cone outer segments appear disorganized
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• marker analysis indicates compromised morphology of rod bipolar cell synapses in the inner plexiform layer
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• rod bipolar cell dendrites extend beyond the outer plexiform layer, far into the outer nuclear layer unlike in wild-type mice where they are restricted to the outer plexiform layer
• horizontal cell neurites extend far into the outer nuclear layer which is not seen in wild-type mice
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• horizontal cell bodies are reduced in the outer plexiform layer and numerous elongated horizontal cell neurites extend far into the outer nuclear layer
• loss of cone pedicles in the outer plexiform layer
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• reactive gliosis in Muller glial cells
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• both in the dark-adapted (scotopic) and light-adapted (photopic) part of the ERG, the b-wave component and oscillatory potentials are completely absent compared to wild-type mice throughout the stimulus range, indicating a defect in neurotransmission from both rod and cone photoreceptors
• however, the amplitude and threshold of the a-wave is similar to wild-type
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• in the vision-guided water-maze task, mice have an increased latency to navigate to a visible platform under both dark and normal light conditions
• in about 38% of the trials in the dark and about 27% of trials during light, mutants do not find the platform within the 2 minute test period compared to wild-type mice which all find the platform
• in contrast to wild-type mice, mutants show no improvement in finding the platform during 3 successive test days under dark or on the 4th test day under normal light
• swimming path of mutants in the vision-guided water-maze task is much longer than in wild-type mice
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• ERG and behavioral tests indicate that mice are essentially blind
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nervous system
|
|
• irregular outgrowth of bipolar cell neurites
|
|
|
• irregular outgrowth of horizontal cell neurites into the outer nuclear layer
|
|
|
• cone outer segments appear disorganized
|
|
|
• marker analysis indicates disturbed synaptic contacts between photoreceptors and second order neurons and indicates a retraction of photoreceptor synapses from the outer plexiform layer into the outer nuclear layer
• loss of cone pedicles in the outer plexiform layer
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Allelic
Composition |
Cacna1ftm1.1Sdie/Cacna1f+
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Genetic
Background |
involves: C57BL/6 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1ftm1.1Sdie mutation
(1 available);
any
Cacna1f mutation
(19 available)
|
|
|
vision/eye
|
|
• retina is mosaic due to differential X-chromosomal inactivation of Cacna1f resulting in vertical columns of affected and nonaffected retinal tissue
• retinal network columns with compromised morphology are radially oriented and display outgrowths of horizontal cell neurites and bipolar cell dendrites into the outer nuclear layer and thinning of the outer plexiform layer
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• irregular outgrowth of bipolar cell dendrites into the outer nuclear layer
|
|
|
• irregular outgrowth of horizontal cell neurites into the outer nuclear layer
|
|
|
• outgrowths of horizontal cell neurites and bipolar cell dendrites into the outer nuclear layer
|
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• reactive gliosis in the affected retinal columns
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• defect in transmission of visual signals from rod and cone photoreceptors to bipolar cells
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• scotopic ERGs are characterized by reduced b-wave amplitudes and oscillatory potentials
• photopic ERGs are characterized by reduced b-wave amplitude
• however, the threshold of the b-wave, and the amplitude and threshold of the a-wave are normal for scotopic ERGs
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• in the vision-guided water-maze task, heterozygous females have an increased latency to navigate to a visible platform under dark conditions compared to wild-type mice but less so than in homozygotes
• under normal light conditions, heterozygotes have only slightly increased latencies and do not make any error of omissions
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nervous system
|
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• irregular outgrowth of bipolar cell dendrites into the outer nuclear layer
|
|
|
• irregular outgrowth of horizontal cell neurites into the outer nuclear layer
|
|
|
• patchy pattern of changes in photoreceptor synaptic morphology
• loss of cone pedicles
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1ftm1.1Sdie mutation
(1 available);
any
Cacna1f mutation
(19 available)
|
|
|
vision/eye
 |
• progressive photoreceptor loss, with rod and cone photoreceptors affected to a similar degree
|
|
|
• moderate reduction in outer nuclear layer (ONL) thickness at 2 and 8 months of age
|
|
|
• increase in the percentage of apoptotic cells in the ONL at P28, however at 2 and 8 months of age, the percentage of apoptotic cells in the retina decreases to wild-type levels, indicating an initial peak of photoreceptor degeneration followed by a steady but moderate degeneration from two months onward
|
|
|
• calcium responses to depolarization of photoreceptor terminals are undetectable
|
|
|
• increase in the percentage of apoptotic cells in the ONL at P28, however at 2 and 8 months of age, the percentage of apoptotic cells in the retina decreases to wild-type levels
|
|
|
• at photopic conditions, flash ERGs are not recordable in mutants
|
|
|
• at scotopic conditions, ERGs display a residual a-wave
|
|
|
• at scotopic conditions, a-wave amplitude is smaller at 2 and 8 months of age
|
|
|
• b-wave in the EEG is absent
|
nervous system
|
|
• progressive photoreceptor loss, with rod and cone photoreceptors affected to a similar degree
|
|
|
• photoreceptor ribbon synapses are abnormal
• cone photoreceptor terminals are either absent or not identifiable as such
• postsynaptic elements and synaptic ribbons are either absent of spherically shaped and free-floating at 2-8 months of age
• the rarely observed anchored rod photoreceptor ribbons are small and club-shaped
|
|
|
• mice exhibit enhanced spouting of rod bipolar- and horizontal cell processes into the ONL already at P14 which peaks at P28 and then declines
|
cellular
|
|
• increase in the percentage of apoptotic cells in the ONL at P28, however at 2 and 8 months of age, the percentage of apoptotic cells in the retina decreases to wild-type levels
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1ftm1.1Sdie mutation
(1 available);
any
Cacna1f mutation
(19 available)
|
|
|
vision/eye
|
|
• irregular outgrowth of bipolar cell neurites
|
|
|
• irregular outgrowth of horizontal cell neurites into the outer nuclear layer
|
|
|
• cone outer segments appear disorganized
|
|
|
• marker analysis indicates compromised morphology of rod bipolar cell synapses in the inner plexiform layer
|
|
|
• rod bipolar cell dendrites extend beyond the outer plexiform layer, far into the outer nuclear layer unlike in wild-type mice where they are restricted to the outer plexiform layer
• horizontal cell neurites extend far into the outer nuclear layer which is not seen in wild-type mice
|
|
|
• horizontal cell bodies are reduced in the outer plexiform layer and numerous elongated horizontal cell neurites extend far into the outer nuclear layer
• loss of cone pedicles in the outer plexiform layer
|
|
|
• reactive gliosis in Muller glial cells
|
|
|
• both in the dark-adapted (scotopic) and light-adapted (photopic) part of the ERG, the b-wave component and oscillatory potentials are completely absent compared to wild-type mice throughout the stimulus range, indicating a defect in neurotransmission from both rod and cone photoreceptors
• however, the amplitude and threshold of the a-wave is similar to wild-type
|
|
|
• in the vision-guided water-maze task, mice have an increased latency to navigate to a visible platform under both dark and normal light conditions
• in about 38% of the trials in the dark and about 27% of trials during light, mutants do not find the platform within the 2 minute test period compared to wild-type mice which all find the platform
• in contrast to wild-type mice, mutants show no improvement in finding the platform during 3 successive test days under dark or on the 4th test day under normal light
• swimming path of mutants in the vision-guided water-maze task is much longer than in wild-type mice
|
|
|
• ERG and behavioral tests indicate that mice are essentially blind
|
nervous system
|
|
• irregular outgrowth of bipolar cell neurites
|
|
|
• irregular outgrowth of horizontal cell neurites into the outer nuclear layer
|
|
|
• cone outer segments appear disorganized
|
|
|
• loss of cone pedicles in the outer plexiform layer
• marker analysis indicates disturbed synaptic contacts between photoreceptors and second order neurons and indicates a retraction of photoreceptor synapses from the outer plexiform layer into the outer nuclear layer
|
Analysis Tools