|
Allele Symbol Allele Name Allele ID |
Cnga3tm1Biel targeted mutation 1, Martin Biel MGI:2388388 |
||||||||||||||||||||||||
| Summary |
5 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as measured by electroolfactogram, uroguanylin- and guanylin-evoked potentials are abolished
|
|
• tyrosine hydrolase immunoreactivity is nearly absent in olfactory bulb periglomular cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Retinal morphology of 2 month old Cnga3tm1Biel/Cnga3tm1Biel and wild-type mice
|
• homozygotes display a a progressive degeneration of cone photoreceptors
• at 2 months, the number of cones is reduced to ~10-20% of wild-type number
• no cone photoreceptors are detected in homozygotes older than 8 months of age
|
|
• in homozygotes, the disks of cone outer segments are partially disorganized
• in contrast, the disks of rod outer segments remain unaffected
|
|
• homozygotes lack cone-mediated light response
• notably, mutant rod photoreceptors are both structurally and functionally intact ("pure rod function")
|
|
• under dark-adapted (scotopic) conditions, the b-wave shows normal thresholds up to ~0.01 cds/m2 intensity; however, b-wave amplitudes of homozygotes do not increase further with flash intensity
• in contrast to the b-wave, the scotopic a-wave does not show any differences over the entire intensity range
• under light-adapted conditions of 30 cd/m2, homozygotes fail to show a perceivable cone response
• in scotopic ERGs induced by trains of flashes (flicker), a low stimulus intensity (0.01 cds/m2) causes a normal pure rod response
• at high stimulus intensity (3 cds/m2), the ERG response of homozygotes is less than normal, even at the lowest frequency; under these conditions the flicker fusion frequency is only ~10% of wild-type
|
|
• homozygotes display a a progressive degeneration of cone photoreceptors
• at 2 months, the number of cones is reduced to ~10-20% of wild-type number
• no cone photoreceptors are detected in homozygotes older than 8 months of age
|
|
• in homozygotes, the disks of cone outer segments are partially disorganized
• in contrast, the disks of rod outer segments remain unaffected
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| achromatopsia 2 | DOID:0110007 |
OMIM:216900 |
J:56020 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• triple mutants essentially show no pupillary reflex in response to intense exposure of light at 480 nm, monochromatic light at other wavelengths (360-660 nm) or intense white light
• on close scrutiny, 2 out of 6 triple mutants displayed a small, very transient pupil constriction in response to bright 480-nm light; however, this was not consistently observed on repeated stimulus trials with extensive dark adaptation (up to 3 days) in between
• in contrast, triple mutants exhibit maximum pupil constriction in response to carbachol (a parasympathetic agonist)
|
|
• actograms of wheel running under a 16/8-h light/dark cycle showed that triple mutants free-run with a period of less than 24 hours
|
|
• triple homozygotes fail to entrain to light/dark cycles and show no masking response to light
|
| N |
• triple homozygotes display normal retinal morphology and thickness relative to wild-type mice
• also, triple mutants show normal abundance and central connectivity of melanopsin-expressing retinal ganglion cells in brain
|
|
• triple mutants essentially show no pupillary reflex in response to intense exposure of light at 480 nm, monochromatic light at other wavelengths (360-660 nm) or intense white light
• on close scrutiny, 2 out of 6 triple mutants displayed a small, very transient pupil constriction in response to bright 480-nm light; however, this was not consistently observed on repeated stimulus trials with extensive dark adaptation (up to 3 days) in between
• in contrast, triple mutants exhibit maximum pupil constriction in response to carbachol (a parasympathetic agonist)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at stimuli ranging from 0.0001 to 25 cds/m2, scotopic single-flash ERGs of double homozygotes are almost identical to those of Rpe65tm1Tmr single mutants, indicating that rods are responsible for the light responses in Rpe65tm1Tmr mutants
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leber congenital amaurosis 2 | DOID:0110016 |
OMIM:204100 |
J:71529 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 9 months, some of the axon terminals of rod bipolar cells have retracted and/or appear swollen; the ribbon synapses are almost absent
• in contrast, the stratification pattern of cone bipolar cell axons and amacrine cell processes appear relatively unaffected
|
|
• at PW5, many of the horizontal cell processes of mutant retinas show extensive sprouting into the ONL and INL
|
|
• at 2 months, the double mutant retina exhibits a massive reduction of the outer nuclear layer, whereas the inner retina remains unaffected
• by 10 months, the outer retina has degenerated completely, whereas the inner retina still appears morphologically intact
• at later stages of retinal degeneration, the inner plexiform layer (IPL) is also affected
|
|
• in double mutants, photoreceptor degeneration begins at ~PW4 and increases rapidly after PW7
• at PW10, the photoreceptor layer is reduced to one row of nuclei; by PW12, the entire ONL is missing in most parts of the retina
|
|
• by PW4, the number of rod spherules is reduced to <50% of wild-type number
• double mutants have rod spherules with 2, 3, or more synaptic ribbons and larger numbers of postsynaptic elements
• at PW4, 45% of mutant rod spherules have 2 or more ribbons, whereas only 4% of wild-type shperules have more than 1 ribbon
• by PW5 and PW6, >80% of the surviving rod spherules contain 2 or more ribbons
|
|
• double mutants exhibit a progressive degeneration of all photoreceptors within 3 months after birth
• notably, double mutants display normal expression of presynaptic markers and postsynaptic glutamate receptors in the outer plexiform layer (OPL) until postnatal week 7 (PW7)
|
|
• at ~P35, scotopic ERGs confirm loss of both rod and cone-driven responses in double homozygotes
|
|
• in double mutants, photoreceptor degeneration begins at ~PW4 and increases rapidly after PW7
• at PW10, the photoreceptor layer is reduced to one row of nuclei; by PW12, the entire ONL is missing in most parts of the retina
|
|
• at 9 months, some of the axon terminals of rod bipolar cells have retracted and/or appear swollen; the ribbon synapses are almost absent
• in contrast, the stratification pattern of cone bipolar cell axons and amacrine cell processes appear relatively unaffected
|
|
• at PW5, many of the horizontal cell processes of mutant retinas show extensive sprouting into the ONL and INL
|
|
• by PW4, the number of rod spherules is reduced to <50% of wild-type number
• double mutants have rod spherules with 2, 3, or more synaptic ribbons and larger numbers of postsynaptic elements
• at PW4, 45% of mutant rod spherules have 2 or more ribbons, whereas only 4% of wild-type shperules have more than 1 ribbon
• by PW5 and PW6, >80% of the surviving rod spherules contain 2 or more ribbons
|
|
• double mutants exhibit a progressive degeneration of all photoreceptors within 3 months after birth
• notably, double mutants display normal expression of presynaptic markers and postsynaptic glutamate receptors in the outer plexiform layer (OPL) until postnatal week 7 (PW7)
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 04/23/2024 MGI 6.23 |
|
|
|
||
Analysis Tools