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Allele Symbol Allele Name Allele ID |
Cetn2tm1.1Wbae targeted mutation 1.1, Wolfgang Baehr MGI:5634782 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• mice exhibit normal body weights and do not develop hydrocephalus, unlike males carrying the Cetn2tm1.1Wbae allele
• mice are rescued from the OSN ciliary trafficking defect, as shown by normal ciliary localizations of two major transmembrane signaling proteins (ACIII and CNGA2), and a peripheral membrane-associated protein
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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
|
|
|
• 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
|
|
|
| ♀ | 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
|
|
|
• 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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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• ~30% of mice develop a dome-shaped skull and die within 1.5 months
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• when heterozygous females are bred with wild-type males, male knockout pups are obtained at slightly lower Mendelian ratios (42.5% versus expected 50%)
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• however, early olfactory ciliogenesis (before P5) appears to be normal
• at P14 or later, Ac-alpha-tubulin (cilium marker) immunolabeling revealed a marked decrease of ciliary layer thickness with Ac-alpha-tubulin-negative spots
• at P16, SEM of OE tissues revealed that cilia are reduced in density, appear short and stubby with slightly enlarged tips, and that several dendritic knobs are enlarged
• OR256-17 immunostaining confirmed significantly reduced knob density, cilium density, and average ciliary length
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
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|
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• as early as P5 (i.e. prior to cilia loss), many OSNs display dendrite and soma mislocalization of the olfactory signaling protein, adenylate cyclase III (ACIII); however, olfactory cilia appear intact at this stage, indicating an OSN ciliary trafficking defect
• as OE develops, the ciliary trafficking defect can be observed in all turbinates and septa
• by P14 or older, immunoreactivity for two major transmembrane signaling proteins, ACIII and CNGA2, show massive mislocalization to OSN dendrites and cell bodies
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• cilia base-anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appears compromised in OSNs
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• at weaning, body weight is ~30% lower than that in wild-type controls
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• although born healthy and of normal size, mice exhibit progressive weight loss
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• at P14 or later, Ac-alpha-tubulin (cilium marker) immunolabeling revealed a marked decrease of ciliary layer thickness with Ac-alpha-tubulin-negative spots
• at P16, SEM of OE tissues revealed that cilia are reduced in density, appear short and stubby with slightly enlarged tips, and that several dendritic knobs are enlarged
• OR256-17 immunostaining confirmed significantly reduced knob density, cilium density, and average ciliary length
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• however, early olfactory ciliogenesis (before P5) appears to be normal
|
|
|
• as early as P5 (i.e. prior to cilia loss), many OSNs display dendrite and soma mislocalization of the olfactory signaling protein, adenylate cyclase III (ACIII); however, olfactory cilia appear intact at this stage, indicating an OSN ciliary trafficking defect
• as OE develops, the ciliary trafficking defect can be observed in all turbinates and septa
• by P14 or older, immunoreactivity for two major transmembrane signaling proteins, ACIII and CNGA2, show massive mislocalization to OSN dendrites and cell bodies
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• cilia base-anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appears compromised in OSNs
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• overnight-fasted mice take over seven times longer to locate food than wild-type controls, suggesting dysosmia
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• electro-olfactograms (EOG) amplitudes are reduced by 48-69% with all tested odorants: 58% reduction for citral, 48% for S-butanol, 61% for acetophenone, 69% for cineole, and 67% for R-carvone
• dose-dependent EOG recordings with amyl acetate revealed amplitude reduction at every tested concentration
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• at P21, Ac-alpha-tubulin immunolabeling revealed that although the density of lateral ventricle ependymal cilia is normal, the orientation of cilia is disrupted with disorganized tufts
• at P16, SEM revealed that ependymal cilia within a tuft, or among adjacent tufts, frequently show variable orientation
• ultrastructurally, P13 basal feet point randomly rather than anteriorly, indicating disrupted rotational planar polarity
• misaligned ependymal cilia are frequently observed, with basal bodies showing two or more electron-dense basal feet
|
|
|
• as early as P5 (i.e. prior to cilia loss), many OSNs display dendrite and soma mislocalization of the olfactory signaling protein, adenylate cyclase III (ACIII); however, olfactory cilia appear intact at this stage, indicating an OSN ciliary trafficking defect
• as OE develops, the ciliary trafficking defect can be observed in all turbinates and septa
• by P14 or older, immunoreactivity for two major transmembrane signaling proteins, ACIII and CNGA2, show massive mislocalization to OSN dendrites and cell bodies
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• cilia base-anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appears compromised in OSNs
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• mice exhibit hydrocephalus of variable severity
• ~30% of mice develop a dome-shaped skull reflecting a dilated brain ventricle; remaining 70% have a normal skull shape but dilated brain ventricles at 10-12 months of age, indicating later onset of hydrocephaly after sealing of cranial suture
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• in mild hydrocephalus, dilation of lateral ventricle is more obvious than that of midbrain aqueduct or fourth ventricle
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• P13 lateral ventricle ependymal cilia generate impaired CSF directional flow, as determined by fluorescent microbead movement in a cilia beating assay
• directional CSF movement is disrupted, slowed, and multidirectional
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• at P14 or later, Ac-alpha-tubulin (cilium marker) immunolabeling revealed a marked decrease of ciliary layer thickness with Ac-alpha-tubulin-negative spots
• at P16, SEM of OE tissues revealed that cilia are reduced in density, appear short and stubby with slightly enlarged tips, and that several dendritic knobs are enlarged
• OR256-17 immunostaining confirmed significantly reduced knob density, cilium density, and average ciliary length
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• however, early olfactory ciliogenesis (before P5) appears to be normal
|
|
|
• ~30% of mice develop a dome-shaped skull reflecting a dilated brain ventricle
|
|
|
• as early as P5 (i.e. prior to cilia loss), many OSNs display dendrite and soma mislocalization of the olfactory signaling protein, adenylate cyclase III (ACIII); however, olfactory cilia appear intact at this stage, indicating an OSN ciliary trafficking defect
• as OE develops, the ciliary trafficking defect can be observed in all turbinates and septa
• by P14 or older, immunoreactivity for two major transmembrane signaling proteins, ACIII and CNGA2, show massive mislocalization to OSN dendrites and cell bodies
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• cilia base-anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appears compromised in OSNs
|
|
|
• ~30% of mice develop a dome-shaped skull reflecting a dilated brain ventricle
|
|
|
• at P14 or later, Ac-alpha-tubulin (cilium marker) immunolabeling revealed a marked decrease of ciliary layer thickness with Ac-alpha-tubulin-negative spots
• at P16, SEM of OE tissues revealed that cilia are reduced in density, appear short and stubby with slightly enlarged tips, and that several dendritic knobs are enlarged
• OR256-17 immunostaining confirmed significantly reduced knob density, cilium density, and average ciliary length
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• however, early olfactory ciliogenesis (before P5) appears to be normal
|
|
|
• as early as P5 (i.e. prior to cilia loss), many OSNs display dendrite and soma mislocalization of the olfactory signaling protein, adenylate cyclase III (ACIII); however, olfactory cilia appear intact at this stage, indicating an OSN ciliary trafficking defect
• as OE develops, the ciliary trafficking defect can be observed in all turbinates and septa
• by P14 or older, immunoreactivity for two major transmembrane signaling proteins, ACIII and CNGA2, show massive mislocalization to OSN dendrites and cell bodies
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• cilia base-anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appears compromised in OSNs
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N |
• respiratory cilia appear to be normal in density and axonemal ultrastructure and show normal localization of cytoplasmic dynein2 and KIF3A at cilia bases
• renal tubule cilia appear normal in morphology and density, as shown by Ac-alpha-tubulin immunostaining
• another type of primary cilium, the ACIII-positive neuronal cilium of the brain, also appears normal in density although ACIII distribution along the cilia is not as smooth as in wild-type controls
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|
|
• at P21, Ac-alpha-tubulin immunolabeling revealed that although the density of lateral ventricle ependymal cilia is normal, the orientation of cilia is disrupted with disorganized tufts
• at P16, SEM revealed that ependymal cilia within a tuft, or among adjacent tufts, frequently show variable orientation
• ultrastructurally, P13 basal feet point randomly rather than anteriorly, indicating disrupted rotational planar polarity
• misaligned ependymal cilia are frequently observed, with basal bodies showing two or more electron-dense basal feet
|
|
|
• at P14 or later, Ac-alpha-tubulin (cilium marker) immunolabeling revealed a marked decrease of ciliary layer thickness with Ac-alpha-tubulin-negative spots
• at P16, SEM of OE tissues revealed that cilia are reduced in density, appear short and stubby with slightly enlarged tips, and that several dendritic knobs are enlarged
• OR256-17 immunostaining confirmed significantly reduced knob density, cilium density, and average ciliary length
• at P14, many dendritic knobs and basal bodies are mislocalized beneath the OE surface, indicating basal body apical migration/docking defects
• however, early olfactory ciliogenesis (before P5) appears to be normal
|
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N |
• at 1 month of age, mice show normal transport of photoreceptor outer segment proteins, including rod and cone visual pigments
• no difference in scotopic ERG a-wave or b-wave amplitude is observed at multiple light intensities
• normal rod transducin localization is observed in dark- or light-adapted retinas
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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 04/30/2024 MGI 6.23 |
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