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Allele Symbol Allele Name Allele ID |
Cetn3tm1a(EUCOMM)Wtsi targeted mutation 1a, Wellcome Trust Sanger Institute MGI:4842368 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are born in a normal Mendelian ratio and are viable and fertile with no evidence of syndromic ciliopathy; retinal photoreceptors show normal electroretinograms and ciliary trafficking with no changes in rod and cone outer segment (OS) protein localization relative to wild-type or heterozygous controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• male pups are obtained at a significantly lower Mendelian ratio (29.2% versus expected 50%) suggesting the some male embryos do not survive prenatal development
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• average litter size is only 5.5 versus 6.8 for single Cetn3tm1a(EUCOMM)Wtsi homozygotes and 6.7 for single Cetn3tm1d(EUCOMM)Wtsi homozygotes
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• at P22, the length of proximal axonemes labeled by RP1 (retinitis pigmentosa 1 protein) is slightly but significantly reduced; by 3 months, RP1+ axoneme length is 56% of that in single Cetn3tm1a(EUCOMM)Wtsi homozygotes
• CETN1 is gradually depleted from the connecting cilium (CC) distal and proximal ends and accumulates in the central CC; the length of the CETN1+ CC fragment is reduced to 78.5% at P25 and to 56.3% by 3 months
• at 3 months but not at P25, the Ac-tubulin signal ratio (at CC versus proximal axoneme) is significantly reduced, indicating a gradual deacetylation of CC microtubules but hyperacetylation of proximal OS axoneme microtubules
• at 2.5 months, ~20-30% of photoreceptors show variable dilation at the distal CC and OS proximal axoneme, ranging from a slight expansion to extreme dilation with invasion of vertically aligned disc membranes and loss of microtubule doublet integrity
• at 2 months, SPATA7 (a key organizer of the photoreceptor-specific distal CC) is partially depleted starting from the CC mid-segment, and by 3 months SPATA7 is almost undetectable along the entire CC length, indicating that distal CC dilation correlates with SPATA7 depletion
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• at 2.5 months of age, OS disc membranes are overgrown and vertically aligned
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• at 2.5 months of age, OS diameters are increased
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• at 3 months but not at 1 month of age, photoreceptor outer segment (OS) length is significantly decreased; OS length is 10-15 um in the ventral retina and only 5-10 um in the dorsal peripheral retina
• by 13 months, only one layer of ONL nuclei remains in the dorsal retina with residual OS/IS; the ventral retina is more stable showing OS of half-normal length
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• at 3 months of age, cone OS is enlarged; a fraction of cone OS is swollen to triple diameter
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• at 2.5 months of age, OS structure is highly disorganized, as shown by overgrown and longitudinally aligned discs, membrane whorls, and expanded OS diameters
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• mice exhibit slow photoreceptor degeneration starting after ~1 month of age and nearing completion in the dorsal retina at 1 year of age
• despite ongoing degeneration, no mislocalization of any rod or cone OS protein is observed at 3 months
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• at 3 months but not at 1 month of age, retinal outer nuclear layer (ONL) thickness is significantly decreased, with 6-7 rows of nuclei (30-35 um) in the ventral retina and 4-5 rows of nuclei (20-25 um) in the dorsal retina
• by 13 months, only one layer of ONL nuclei remains in the dorsal retina with residual OS/IS compared with 4-5 layers of nuclei in the ventral ONL
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• at 3 months of age, scotopic a-wave amplitudes are significantly smaller than the corresponding amplitudes in single Cetn3tm1a(EUCOMM)Wtsi homozygotes at multiple light intensities (0.6, 0.4, and 2.4 log cd s/m2)
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• at 3 months of age, scotopic b-wave amplitudes are significantly smaller than the corresponding amplitudes in single Cetn3tm1a(EUCOMM)Wtsi homozygotes at all light intensities tested (1.6, 0.6, 0.4, and 2.4 log cd s/m2)
• at 3 months of age, photopic b-wave amplitudes are significantly smaller than those in single Cetn3tm1a(EUCOMM)Wtsi homozygotes at multiple light intensities (0.4, 0.9, 1.4, and 1.9 log cd s/m2)
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• at 3 months of age, the photopic ERG response is significantly reduced relative to that in single Cetn3tm1a(EUCOMM)Wtsi homozygotes
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• at 3 months of age, the scotopic ERG response is significantly reduced relative to that in single Cetn3tm1a(EUCOMM)Wtsi homozygotes
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• at P22, the length of proximal axonemes labeled by RP1 (retinitis pigmentosa 1 protein) is slightly but significantly reduced; by 3 months, RP1+ axoneme length is 56% of that in single Cetn3tm1a(EUCOMM)Wtsi homozygotes
• CETN1 is gradually depleted from the connecting cilium (CC) distal and proximal ends and accumulates in the central CC; the length of the CETN1+ CC fragment is reduced to 78.5% at P25 and to 56.3% by 3 months
• at 3 months but not at P25, the Ac-tubulin signal ratio (at CC versus proximal axoneme) is significantly reduced, indicating a gradual deacetylation of CC microtubules but hyperacetylation of proximal OS axoneme microtubules
• at 2.5 months, ~20-30% of photoreceptors show variable dilation at the distal CC and OS proximal axoneme, ranging from a slight expansion to extreme dilation with invasion of vertically aligned disc membranes and loss of microtubule doublet integrity
• at 2 months, SPATA7 (a key organizer of the photoreceptor-specific distal CC) is partially depleted starting from the CC mid-segment, and by 3 months SPATA7 is almost undetectable along the entire CC length, indicating that distal CC dilation correlates with SPATA7 depletion
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• mice surviving to adulthood display hydrocephalus
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• at 2.5 months of age, OS disc membranes are overgrown and vertically aligned
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• at 2.5 months of age, OS diameters are increased
|
|
|
• at 3 months but not at 1 month of age, photoreceptor outer segment (OS) length is significantly decreased; OS length is 10-15 um in the ventral retina and only 5-10 um in the dorsal peripheral retina
• by 13 months, only one layer of ONL nuclei remains in the dorsal retina with residual OS/IS; the ventral retina is more stable showing OS of half-normal length
|
|
|
• at 3 months of age, cone OS is enlarged; a fraction of cone OS is swollen to triple diameter
|
|
|
• at 2.5 months of age, OS structure is highly disorganized, as shown by overgrown and longitudinally aligned discs, membrane whorls, and expanded OS diameters
|
|
|
• mice exhibit slow photoreceptor degeneration starting after ~1 month of age and nearing completion in the dorsal retina at 1 year of age
• despite ongoing degeneration, no mislocalization of any rod or cone OS protein is observed at 3 months
|
|
|
• at P22, the length of proximal axonemes labeled by RP1 (retinitis pigmentosa 1 protein) is slightly but significantly reduced; by 3 months, RP1+ axoneme length is 56% of that in single Cetn3tm1a(EUCOMM)Wtsi homozygotes
• CETN1 is gradually depleted from the connecting cilium (CC) distal and proximal ends and accumulates in the central CC; the length of the CETN1+ CC fragment is reduced to 78.5% at P25 and to 56.3% by 3 months
• at 3 months but not at P25, the Ac-tubulin signal ratio (at CC versus proximal axoneme) is significantly reduced, indicating a gradual deacetylation of CC microtubules but hyperacetylation of proximal OS axoneme microtubules
• at 2.5 months, ~20-30% of photoreceptors show variable dilation at the distal CC and OS proximal axoneme, ranging from a slight expansion to extreme dilation with invasion of vertically aligned disc membranes and loss of microtubule doublet integrity
• at 2 months, SPATA7 (a key organizer of the photoreceptor-specific distal CC) is partially depleted starting from the CC mid-segment, and by 3 months SPATA7 is almost undetectable along the entire CC length, indicating that distal CC dilation correlates with SPATA7 depletion
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• at 3 months of age, scotopic b-wave amplitude is significantly smaller than that in single Cetn3tm1a(EUCOMM)Wtsi homozygotes at 1.4 log cd s/m2
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• at 3 months of age, mice show an intermediate reduction in the scotopic ERG response at multiple light intensities
• although both scotopic a-wave and b-wave amplitudes are smaller than those in single Cetn3tm1a(EUCOMM)Wtsi homozygotes, these reductions are not statistically significant at most light intensities tested
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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 05/07/2024 MGI 6.23 |
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