Analysis Tools
vision/eye
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• rods are reprogrammed into cones
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nervous system
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• rods are reprogrammed into cones
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Allele Symbol Allele Name Allele ID |
Nrltm1Asw targeted mutation 1, Anand Swaroop MGI:2152376 |
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| Summary |
8 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Adult rods are reprogrammed into cone-like cells in Nrltm1.1Jcco/Nrltm1.1Jcco and Nrltm1Asw/Nrltm1Asw retinas
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• rods are reprogrammed into cones
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• rods are reprogrammed into cones
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• visually guided behavior testing (optokinetic reflex) shows decreased cone-mediated spatial frequency thresholds with mice losing the ability to track at 6 months of age
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• abnormal retinal lamination is seen at 4 weeks of age
• abnormal intraretinal hyperreflective lesions
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• retina shows aberrant photoreceptor packing, with aberrant clustering of photoreceptors with empty patches where nuclear rosettes form, and abnormal association with the retinal pigment epithelium
• abnormal buildup of material in photoreceptors is seen at the photoreceptor-retinal pigment epithelium interface
• photoreceptors are not tightly packed at the retinal pigment epithelium interface
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• outer segment of photoreceptors appears bulbous and outer segment tips are enlarged due to an internal buildup of vacuole-like structures
• photoreceptors show an outer segment disc arrangement different from rods, with some discs showing interconnections to each other and the surrounding plasma membrane
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• excessive S-cone photoreceptors exhibit abnormal accumulations of materials
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• excessive S-cone photoreceptor population
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• photoreceptor degeneration is seen by 8 weeks of age
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• 6 month old mice have fewer cones in the inferior versus superior retinas
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• severely reduced retinal pigment epithelium interface phagocytosis of outer segment, with lack of phagosomes in the retinal pigment epithelium
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• severely reduced retinal pigment epithelium interface phagocytosis of outer segment
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• M-cone responses are decreased in 2 and 6 month old mice
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• severely reduced retinal pigment epithelium interface phagocytosis of outer segment, with lack of phagosomes in the retinal pigment epithelium
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• retina shows aberrant photoreceptor packing, with aberrant clustering of photoreceptors with empty patches where nuclear rosettes form, and abnormal association with the retinal pigment epithelium
• abnormal buildup of material in photoreceptors is seen at the photoreceptor-retinal pigment epithelium interface
• photoreceptors are not tightly packed at the retinal pigment epithelium interface
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• outer segment of photoreceptors appears bulbous and outer segment tips are enlarged due to an internal buildup of vacuole-like structures
• photoreceptors show an outer segment disc arrangement different from rods, with some discs showing interconnections to each other and the surrounding plasma membrane
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• excessive S-cone photoreceptors exhibit abnormal accumulations of materials
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• excessive S-cone photoreceptor population
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• photoreceptor degeneration is seen by 8 weeks of age
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• 6 month old mice have fewer cones in the inferior versus superior retinas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| enhanced S-cone syndrome | DOID:0090059 |
OMIM:268100 |
J:175566 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mutant photoreceptor nuclei were ellipsoid and showed a distributed pattern of heterochromatin, characteristic of cones
(J:78692)
• immunohistochemistry revealed normal M-opsin distribution but no rhodopsin immunoreactivity; S-opsin was detected throughout the outer segments, indicating a loss of rod and 'gain' of S- but not M-cone activity
(J:78692)
• analysis of "pure-cone" retinas demonstrated that both S and M cone opsins were phosphorylated after light exposure and that cone arrestin selectively bound to light-activated, phosphorylated cone opsins
(J:84455)
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• the outer segments were significantly fewer and shorter and showed abnormal disk morphology; also, the outer segment disks were often misaligned and abnormally associated with the retinal pigment epithelium
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• at 5 weeks, the outer nuclear layer (ONL) of the mutant retina had a normal thickness and number of nuclei but appeared to be disrupted with whorls and rosettes
• by 31 weeks, the rosettes and whorls were no longer detectable and thinning of the ONL had occurred
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• overexpress S opsin with an abnormal distribution
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• in light-adapted conditions, the b-wave threshold was the same for wild-type and mutant mice, indicating a functional cone pathway in the mutant retina
• notably, the amplitude of the maximum light-adapted ERG b-wave for mutant mice was 2-3-fold larger relative to wild-type, indicating enhanced cone-mediated activity
• ERGs using monochromatic stimuli revealed that the amplitude of the S cone-mediated response was >6 times larger for mutant mice than for wild-type, suggesting a super-normal S-cone function; in contrast, the M-cone response was relatively unaffected
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• ERGs from dark-adapted mutant mice revealed a complete absence of rod function ("pure-cone" retinas)
(J:78692)
• lack scotopic ERG responses
(J:174592)
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• most mutant photoreceptor nuclei were ellipsoid and showed a distributed pattern of heterochromatin, characteristic of cones
(J:78692)
• immunohistochemistry revealed normal M-opsin distribution but no rhodopsin immunoreactivity; S-opsin was detected throughout the outer segments, indicating a loss of rod and 'gain' of S- but not M-cone activity
(J:78692)
• analysis of "pure-cone" retinas demonstrated that both S and M cone opsins were phosphorylated after light exposure and that cone arrestin selectively bound to light-activated, phosphorylated cone opsins
(J:84455)
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• the outer segments were significantly fewer and shorter and showed abnormal disk morphology; also, the outer segment disks were often misaligned and abnormally associated with the retinal pigment epithelium
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 6 month old mice have fewer cones in the inferior versus superior retinas
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• outer nuclear layer (ONL) is 28% thinner than in single Nrl homozygotes at 6 months of age
• treatment with an adenovirus expressing Gucy2e results in cone preservation with increased ONL thickness
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• ERG indicates no discernible wave forms, with no M-cone or S-cone responses
• subretinal injection of an adenovirus expressing Gucy2e at around P41, but not at P18, fully restores retinal function and useful vision over the long-term
• mice treated with an adenovirus expressing human GUCY2D at P40 exhibit restored retinal function
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• visually guided behavior testing (optokinetic reflex) shows decreased cone-mediated spatial frequency thresholds at 6 months of age
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• no retinal guanylate cyclase activity in the retina
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• 6 month old mice have fewer cones in the inferior versus superior retinas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leber congenital amaurosis 1 | DOID:0110078 |
OMIM:204000 |
J:241970 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show degeneration of photoreceptors, with rapid loss of rods, however survival of cone photoreceptors is increased compared to single Cep290 mutants, showing 4-5 rows of outer nuclear layer nuclei at 3-4 months of age, indicating a much slower cone degeneration than in single mutants and an all-cone retina in mutants
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• mice show sizeable S- and M-cone-driven ERG signals although the amplitudes are reduced compared to single Nrl homozygotes
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• mice show degeneration of photoreceptors, with rapid loss of rods, however survival of cone photoreceptors is increased compared to single Cep290 mutants, showing 4-5 rows of outer nuclear layer nuclei at 3-4 months of age, indicating a much slower cone degeneration than in single mutants and an all-cone retina in mutants
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Leber congenital amaurosis 10 | DOID:0110291 |
OMIM:611755 |
J:169232 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cone outer segment tips are larger than in single Nrl mutants
• no cone phagosomes are seen in the outer segment
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• cone outer segment tips are larger than in single Nrl mutants
• no cone phagosomes are seen in the outer segment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cone outer segment tips are larger than in single Nrl mutants
• no cone phagosomes are seen in the outer segment
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• no cone phagosomes are seen in the outer segment
• cone outer segment tips are larger than in single Nrl mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in situ light-dependent phosphorylation of opsins ex vivo showed that neither S nor M opsin was phosphorylated in the double mutant mouse retina after light exposure
• however, retinas of double mutant mice displayed the same morphology as those of single Nrl mutant mice, and both S and M opsins were expressed in the double mutant retina at equivalent levels to those in single Nrl mutant retina
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• in situ light-dependent phosphorylation of opsins ex vivo showed that neither S nor M opsin was phosphorylated in the double mutant mouse retina after light exposure
• however, retinas of double mutant mice displayed the same morphology as those of single Nrl mutant mice, and both S and M opsins were expressed in the double mutant retina at equivalent levels to those in single Nrl mutant retina
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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 04/09/2024 MGI 6.23 |
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