vision/eye
• 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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cellular
• 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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nervous system
• 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 |