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Allele Symbol Allele Name Allele ID |
Crb2tm1.1Wij targeted mutation 1.1, Jan Wijnholds MGI:5466324 |
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| Summary |
8 genotypes
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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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• subretinal delivery of a cre-expressing adenovirus results in ectopic photoreceptor nuclei protruding into the subretinal space
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• retinas from mice with subretinal delivery of a Cre-expressing adenovirus show disruptions of the outer plexiform layer
• subretinal delivery of a photoreceptor-specific Grk1 promoter driven Cre-expressing adenovirus results in small morphological abnormalities in the retina such as disruptions of the outer plexiform layer
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• morphological alterations after E18.5
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• numerous large retinal blood vessels by 12 months of age
• sites of neovascularization by 3 months of age, sometimes with choroidal structures
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• misplaced bipolar cell nuclei in the outer nuclear layer
• cells possess fewer dendrites than in controls
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• disruption of the retinal pigment layer by 3 months
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• reduced retinal thickness in the outer retina and cellular mislocalization
• most severe degeneration in the central retina
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• normal orientation of photoreceptors is lost
• rosettes and half rosettes found in the periphery of the retina
• ectopic nuclei in subretinal space at 10 days of age, do not develop proper segments
• loss of adherens junctions near ectopic cells
• increased apoptosis between 3 and 21 days
• apoptosis level peaks around 15 days
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• very few photoreceptor cells by 12 months
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• cone cells also displaced to sub retinal space
• polarity defects
• cone outer segments shorter than in controls
• cells survive to 3 months but with loss of segments
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• sporadic disruptions of the outer limiting membrane
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• indications of progressive retinal degeneration by 1 month of age
• accumulation of autofluorescent remains of lost photoreceptor cells
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• progressive signal amplitude reduction with age to near extinction at 18 months of age
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• reduced amplitude of photopic electroretinography responses
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• reduced amplitude of scotopic electroretinography responses
• greater attenuation of a-waves relative to b-waves at high stimulus intensities (higher b/a ratio)
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• very few photoreceptor cells by 12 months
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• misplaced bipolar cell nuclei in the outer nuclear layer
• cells possess fewer dendrites than in controls
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• cone cells also displaced to sub retinal space
• polarity defects
• cone outer segments shorter than in controls
• cells survive to 3 months but with loss of segments
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• disruption of the retinal pigment layer by 3 months
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• numerous large retinal blood vessels by 12 months of age
• sites of neovascularization by 3 months of age, sometimes with choroidal structures
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinitis pigmentosa | DOID:10584 |
OMIM:PS268000 |
J:191149 | |
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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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• mice are born at a 5-fold reduced ratio than expected
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• protrusion of photoreceptor nuclei into the subretinal space at sites of outer limiting membrane disruption at 5 months of age
• however, 5 month old mice show normal electroretinography (ERG), scanning laser ophthalmoscopy, and spectral domain optical coherence tomography readings
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• ectopic Muller glial cell nuclei in the outer nuclear layer and activated Muller glial cells are seen at 5 months of age
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• at 5 months of age, a reduction of the outer nuclear layer thickness is seen
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• disruptions of the outer limiting membrane at the periphery of the retina, where rows of photoreceptor nuclei protrude into the subretinal space, are seen at 1, 3, and 5 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• between E15.5 and E17.5, the adherens junctions are gradually lost in the neural retina
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• increase in the number of Sox9-positive Muller cells
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• increase in the number of GABAergic amacrine cells and late born GlyT1 positive amacrine cells
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• increase in the number of Chx10-positive bipolar cells
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• increase in population of late progenitor cells and late born cells due to dysregulation of the cell cycle at E17.5
• between E15.5 and E17.5, the nuclei of the retinal progenitors show abnormal orientation
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• aberrant layering in the retina is seen at 1 month of age, with a single inner plexiform layer, an abnormal thick ganglion cell layer and a second broad nuclear layer
• all retinal cell types are generated but a separate photoreceptor nuclear layer, inner and outer segment layer and outer plexiform layer are not formed
• cellular mislocalization of late born cells (rod photoreceptors, Muller cells, and bipolar cells) near the retinal pigment epithelium are seen at E13.5
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• no distinct photoreceptor layer is formed at P5
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• increase in the number of rods at P10
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• severe disorganization of the retina
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• the outer limiting membrane is perturbed at E13.5
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• retinal vasculature defects leading to the thinning of the retinas at 3-6 months of age
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• increase in retina thickness at P10 and P14 due to excessive proliferation of late-born retinal progenitor cells
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• retinas degenerate rapidly after 1 month
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• from E15.5 onwards, the number of M-phase cells is increased in retinas
• proportion of retinal cells in G1 is reduced and proportion of cells in S and G2/M is increased at E17.5, however at P1 and P5, cells return to normal cell cycle
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• increase in the number of apoptotic cells in the retinas at P10 and P14 (rod photoreceptors), and 3 months (bipolar cells)
• the number of apoptotic cells in the retina is increased at E13.5 and E17.5 onwards
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• mice exhibit a greater reduction in amplitudes of electroretinogram responses at 1 month of age than single Crb2 conditional mutants, with both scotopic and photopic responses
• electroretinogram responses are below detection at 3 and 6 months of age
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• increase in the number of apoptotic cells in the retinas at P10 and P14 (rod photoreceptors), and 3 months (bipolar cells)
• the number of apoptotic cells in the retina is increased at E13.5 and E17.5 onwards
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• increase in the number of Sox9-positive Muller cells
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• increase in the number of GABAergic amacrine cells and late born GlyT1 positive amacrine cells
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• increase in the number of rods at P10
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• increase in the number of Chx10-positive bipolar cells
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leber congenital amaurosis 8 | DOID:0110079 |
OMIM:613835 |
J:207895 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P5, there is a decrease in the number of apoptotic cells in the retina
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• the number of apoptotic cells is increased in the retina at E17.5
• however, at P5, there is a decrease in the number of apoptotic cells
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• many spots and patchy areas are visible throughout the retina (pseudo-rosettes)
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• disruption of the apical adherens junctions/subapical region in retinas at E15.5 which leads to ectopic localization of some photoreceptor and bipolar cells in the ganglion cell layer and ganglion, amacrine, and bipolar cells in the outer nuclear layer
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• ganglion cell nuclei and inner nuclear layer cells are seen in the outer nuclear layer and some photoreceptor nuclei are seen in the ganglion cell layer
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• rods, cones and bipolar cells localize ectopically in the ganglion cell layer
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• amacrine and ganglion cells surrounded by bipolar cells form pseudo-rosettes in the photoreceptor layer
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• the outer limiting membrane is perturbed at the periphery of the retina at E15.5, and progressively extends to the center of the retinas where rosettes form
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• the number of mitotic cells is increased in the retina at E17.5 and at P5
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• at P5, there is a decrease in the number of apoptotic cells in the retina
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• the number of apoptotic cells is increased in the retina at E17.5
• however, at P5, there is a decrease in the number of apoptotic cells
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• mice exhibit a greater reduction in amplitudes of electroretinogram responses at 1 month of age than single Crb2 conditional mutants, with both scotopic and photopic responses
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leber congenital amaurosis 8 | DOID:0110079 |
OMIM:613835 |
J:207895 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 42% incidence of severe hydrocephalus
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• ventricles of newborns with hydrocephalus are dilated and the subventricular structures are severely damaged
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• disruption of the apical end-feet of Muller glial cells at 3 months of age
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• at 3 months of age, some areas show rod photoreceptors with short or absent outer segments and rhodopsin accumulation in the cell soma
• rod bipolar cells are misplaced in the outer nuclear layer in areas with photoreceptor protrusions at 3 months of age
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• at 3 months of age, the cones show absence of or shortened outer segments and some of the nuclei are displaced to a basal part of the outer nuclear layer, close to the outer plexiform layer
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• several spots and patchy areas are seen in fundus imaging of 1 month old mice
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• lamination of the retina at P10 is severely affected and reduction of the thickness of the outer retina is seen at 1 month of age
• distribution and localization of adherens junctions in the retina are irregular at P3
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• retinal vasculature is abnormal at 1 month of age, with mice showing sites of neovascularization
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• disruption of the apical end-feet of Muller glial cells at 3 months of age
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• protrusion of photoreceptor cells into the subretinal space is seen as early as P1, P3 and P10 and misplaced inner retinal cells in the neuroepithelial layer and adjacent to the retinal pigment epithelium are seen at E18.5
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• misplaced inner retinal cells in the neuroepithelial layer and adjacent to the retinal pigment epithelium are seen at E18.5
• microvilli from the retinal epithelium cells are compressed between the ectopic photoreceptor nuclei and the apical membrane of the retinal pigment epithelium at P3
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• at P10, ectopic nuclei are seen in the ganglion cell layer
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• at 1 and 3 months of age, some residual large photoreceptor rosettes and retinal folds are seen in the outer nuclear layer
• ectopic Sox9-positive Muller glial cell nuclei are seen it the top of the outer nuclear layer
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• the outer nuclear layer is reduced to 4-6 rows of photoreceptor nuclei at 3 months of age
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• the outer plexiform layer is fragmented at 3 months of age
• misplaced inner retinal cells in the outer plexiform layer at 1 month of age
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• at P3, rosettes composed of photoreceptor cells in the middle of the neuroepithelial layer and rosettes composed of inner retinal cells at the top of the neuroepithelial layer are seen in the periphery of the retina
• photoreceptor rosettes are occasionally seen in the neuroepithelial layer at the periphery of the retina as early as E15.5
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• at 3 months of age, some areas show rod photoreceptors with short or absent outer segments and rhodopsin accumulation in the cell soma
• rod bipolar cells are misplaced in the outer nuclear layer in areas with photoreceptor protrusions at 3 months of age
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• at 3 months of age, the cones show absence of or shortened outer segments and some of the nuclei are displaced to a basal part of the outer nuclear layer, close to the outer plexiform layer
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• disruptions of the outer limiting membrane are seen at the periphery as early as E18.5 and P3
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• progressive retinal degeneration is seen with increasing age, characterized by an increase in the number of fundus abnormalities and a more pronounced thinning of the retina
• at 5 months of age, some areas of the retina exhibit regions devoid of photoreceptors
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• at 1 and 3 months of age, some retinal folds are seen in the outer nuclear layer
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• by 1 month of age, retinas show a reduction in both scotopic and photopic ERG amplitudes, indicating altered rod and cone physiology
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• at high stimulus intensities under scotopic conditions, the a-wave is more reduced than the b-wave, resulting in a high b/a ratio and indicating a primary defect in photoreceptors
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• retinal vasculature is abnormal at 1 month of age, with mice showing sites of neovascularization
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• misplaced inner retinal cells in the neuroepithelial layer and adjacent to the retinal pigment epithelium are seen at E18.5
• microvilli from the retinal epithelium cells are compressed between the ectopic photoreceptor nuclei and the apical membrane of the retinal pigment epithelium at P3
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinitis pigmentosa | DOID:10584 |
OMIM:PS268000 |
J:210675 | |
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 05/07/2024 MGI 6.23 |
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