Analysis Tools
vision/eye
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• ~80% reduction in eye volume at age P21
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Allele Symbol Allele Name Allele ID |
Tg(Pax6-cre,GFP)1Pgr transgene insertion 1, Peter Gruss MGI:3045749 |
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| Summary |
25 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• ~80% reduction in eye volume at age P21
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• exhibit a persistent lens stalk at E13.5, E14.5 and even P0
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• arrest of lens fiber cell maturation at the bow-region stage
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• increase in apoptotic cells in the lens results in a smaller lens size
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5, lens reduction is more severe that in either single cre cross but not as severe as in the Pygo2 null homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• beginning at E9.5, lens induction is abnormal as indicated by reduced Pax6+ cells
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• at E9.5, the lens placode is thinner
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• at E12.5, the pigmented epithelium is collapsed to the center of the eye cup
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• at E12.5, lenses were small or absent
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• at E10.5, the optic pit is smaller than normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 1 month of age
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• although born with normal lenses, mice exhibit lens degeneration after 1 month unlike wild-type mice
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• at 1 month of age, fiber cells are swollen and disorganized with many apoptotic nuclei unlike in wild-type mice
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• at 1 month of age
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• at 1 month of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5, lenses were small compared to normal but not as severe as in Pygo2 null homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• axons in the optic nerve are arranged less densely than in controls
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• optic nerves exhibit degenerating axons at 6 months of age, but not at 4 weeks of age, forming dense and irregular whorls of myelin
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• optic nerves are about 30-35% smaller in area and contain fewer axons than controls
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• axons in the optic nerve are arranged less densely than in controls
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• optic nerves exhibit degenerating axons at 6 months of age, but not at 4 weeks of age, forming dense and irregular whorls of myelin
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• optic nerves are about 30-35% smaller in area and contain fewer axons than controls
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• differentiation of trabecular meshwork and Schlemm's canal does not occur and they are absent in the eyes of 3 month old mutants, resulting in complete closure of the iridocorneal angle due to the attachment of the root of the iris to the cornea
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• differentiation of Schlemm's canal does not occur and is absent in the eyes of 3 month old mutants
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• differentiation of trabecular meshwork does not occur and is absent in the eyes of 3 month old mutants
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• in the center of the cornea, where the lens stalk persists and the corneal endothelium is not formed, the anterior tip of the iris remains attached to the inner side of the cornea
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• mice exhibit a central corneal stroma defect in which the corneal epithelium extends to come into contact with the anterior lens capsule and the corneal endothelium is missing in this area
• in some mice, a vesicle surrounded by epithelial cells is seen in the middle of the central corneal stroma
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• in newborns, the lens does not separate from the lens stalk and remains attached to the cornea throughout the first postnatal days but does detach by the third postnatal week
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• intraocular pressure in the eye is elevated
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| juvenile glaucoma | DOID:1068 |
OMIM:137750 |
J:163191 | |
| Peters anomaly | DOID:0060673 |
OMIM:604229 |
J:163191 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E14.5 and P0, lacrimal gland development is disrupted compared to in wild-type mice
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• at E14.5 and P0, lacrimal gland development is disrupted compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in all mice
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• in all mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced in 50% of newborn mice due to impaired budding and defective cell proliferation
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• in 46% of mice
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• reduced in 50% of newborn mice due to impaired budding and defective cell proliferation
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• in 46% of mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P0, corneas are densely covered with lymphatic vessels unlike in wild-type mice
• however, mice exhibit normal limbal blood vessels and corneal hemangiogenesis in response to suture injury
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• hyperplastic lymphatic vessels in the cornea lack erythocytes, do not have a continuous basement membrane, and containing partly overlapping thin endothelial cells free of pericyte coverage unlike wild-type lymphatic vessels
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• at P0, corneas are densely covered with lymphatic vessels unlike in wild-type mice
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• hyperplastic lymphatic vessels in the cornea do not have a continuous basement membrane unlike wild-type lymphatic vessels
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mutant pups die 3 - 6 days after birth with an overt diabetic phenotype
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• very few alpha cells are seen
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• the number of insulin-expressing cells is decreased
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• 2 - 6 days after birth mutant pups develop severe growth retardation
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• 2 - 6 days after birth mutant pups develop hyperglycemia
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• 2 - 6 days after birth mutant pups develop hypoinsulinemia with insulin levels in the pancrease at 18% of normal on P1 and 6% of normal on P3
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• at P3 ketones are seen in all mutants with glucose levels above 20mM
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• lens induction occurs but no thickening or invagination of the surface ectoderm is seen indicating that the lens placode fails to form
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• the optic cup does not form; however, at E11 multiple folds are seen in the neuroretina each developing into a separate retina domain
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• at E10 - E10.5 invagination of the distal wall of the optic vesicle does not occur
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hyperplastic, occludes the pupil
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• irregularly arranged and squamous cells instead of stratified cuboidal cells
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• misshapen, small and vacuolated with central opacity
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• squamous rather than cuboidal cells with loss of E-cadherin early in development
• cells acquire mesenchymal traits
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some embryos injected with tamoxifen early show defective forebrain patterning
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• when tamoxifen is given at E7.5 and 8.5, no thickening or invagination of the PLE is observed at least in one side
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no changes in proliferation or apoptosis are detected in the eye
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• severely disorganized
• accumulation of mesenchymal and vascular cells in the posterior area of the cornea
• expression analysis indicates squamous metaplasia with loss of specific corneal epithelial identity
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• increased cellularity and abnormal cellular arrangements at E14.5
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• lens degeneration
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• viable and fertile, without any overt endocrine phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lens phenotype are less severe than in Tg(Cryaa-NCOA6*)AD5Cve mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, the mutant corneal stroma is thinner with relatively fewer keratocytes relative to wild-type and single Klf5 conditional knockout corneas
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• mutant eyes fail to open as late as 35 weeks after birth, the latest stage examined
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• co-ablation of Klf4 and Klf5 in the ocular surface results in more severe eyelid and corneal abnormalities than those in either single conditional knockout
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• at 8 weeks of age, the mutant conjunctival epithelium is thinner than the wild-type or single Klf5 conditional knockout epithelium
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• at 8 weeks of age, conjunctiva goblet cells are missing
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• at 8 weeks of age, the mutant corneal epithelium is thinner than the wild-type and single Klf5 conditional knockout corneal epithelia, and remains fused to the eyelids
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lenses at E12.5 are smaller but appear normal
• however, mice show well-formed eye structures at E12.5, the presence of optic cup and stalk, and the emerging retinal and pigmented epithelial layers from the optic cup appear normal and mice do not exhibit coloboma
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, adult mutants display inflammation of the eyelids
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• at 8 weeks of age, enucleated mutant eyeballs appear marginally smaller and show a rough and speckled surface, unlike controls
• however, no major difference in eyelid fusion or the structure of the developing eye are noted at P1
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• at 8 weeks of age, about 20% of mutant eyes exhibit a hyperplastic iris causing the pupil to be smaller or absent in some eyes
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• at 8 weeks of age, about 20% of mutant eyes exhibit a hyperplastic iris
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• at 8 weeks of age, the conjunctiva lacks goblet cells, unlike in control mice
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• TEM shows that the basement layer beneath the epithelial cells is thinner in mutant corneas
• fewer and less-electron-dense hemidesmosomes connecting the basal epithelial cells to the basement membrane are observed in mutant corneas
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• at 8 weeks of age, the corneal endothelial cells are swollen and highly vacuolated
• however, the Descemet's membrane appears normal
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• epithelial bulli are occasionally observed in mutant corneas
• TEM indicates fewer corneal epithelium cell layers, fewer microvilli on the superficial cells, as well as swollen, spherical, and vacuolated basal cells, and a higher frequency of delamination than wild-type cells
• SEM of the corneal surface shows a mix of electron-dense and light cells, unlike the uniformly stained cells seen at the wild-type corneal surface
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• at 8 weeks of age, the corneal epithelium has 3 to 4 instead of the normal 5 to 8 cell layers
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• at 8 weeks of age, the corneal stroma is edematous, unlike in controls
• expression of the aquaporin-5 gene is downregulated, consistent with stromal edema
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• in the anterior stroma, the mean number of collagen fibrils per unit cross-sectional is reduced to ~70% of the wild-type number, resulting in higher interfibrillar space, consistent with stromal edema
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• at 8 weeks of age, the mean corneal stroma thickness is increased by 45%
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• at 8 weeks of age, the anterior cortical lens is vacuolated, unlike in control mice
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• at 8 weeks of age, the mutant lens shows vacuolated anterior cortical lens fiber cells beneath the epithelium, extending to the bow region, unlike the compactly packed fiber cells seen in the wild-type lens
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• at 8 weeks of age, the mean size of the mutant lens is decreased by about 12%
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• at 8 weeks of age, the mean size of the mutant eye is decreased by about 12%
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• a 2-fold increase in the number of BrdU-incorporating cells is noted in the corneal epithelium, suggesting that the reduced number of corneal epithelial cell layers is due to excessive cell sloughing rather than a reduced rate of cell proliferation
• expression of the keratin-12 gene is downregulated, consistent with corneal epithelial fragility
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• at 8 weeks of age, adult mutants display inflammation of the eyelids
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lens phenotype are less severe than in Tg(Cryaa-NCOA6*)AD5Cve mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E14.5, the presumptive lacrimal gland precursor remains a thin layer of epithelial cells with little proliferation and no budding unlike in wild-type mice
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• at E14.5, mutants never develop lacrimal buds
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• at E14.5, the presumptive lacrimal gland precursor remains a thin layer of epithelial cells with little proliferation and no budding unlike in wild-type mice
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• at E14.5, mutants never develop lacrimal buds
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, mutant lacrimal glands display numerous infiltrating cells, indicating inflammation
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• at 8 weeks of age, a thicker extra-ocular muscle is observed
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• >80% of adult mutant eyes are small and contain a hypertrophic iris
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• >80% of adult mutant eyes exhibit small pupils
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• frequent iridocorneal fusion is observed
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• frequent iridolenticular fusion is observed
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• at 8 weeks of age, a rough and translucent cornea is observed
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• mutant corneas are thicker than wild-type at P6, P11, P21 and at 10 weeks of age
• however, corneas appear normal at E13.5, E15.5 and E18.5
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• mutant corneal stroma is relatively more intensely stained by PAS, suggesting increased levels of proteoglycans
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• postnatal mutant corneal stroma is hypercellular
• at 8 weeks of age, central corneal stromal thickness and cell density are increased
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• at 8 weeks of age
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• mutant lenses appear spongy and deformed at P6, P11, P21 and at 10 weeks of age
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• at E18.5 and P1, mutant lenses contain significantly fewer epithelial cells in the central anterior region than wild-type controls
• also, fewer and abnormally arranged nuclei are observed in the differentiating equatorial region
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• although mutant primary lens fiber cells appear normal at E13.5 and E15.5, nuclei in E18.5 and P1 lens equatorial regions are disorganized, suggesting defects in secondary fiber formation
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• >80% of postnatal mutant lenses are smaller than wild-type
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• at 8 weeks of age, the enucleated mutant eyeballs are relatively smaller than wild-type
• small eyes are noted at P6, P11, P21 and at 10 weeks of age
• >80% of adult mutant eyes show a small eye phenotype
• however, early eye development is relatively normal
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• mutant eyelids contain significantly enlarged hair follicles and sebaceous glands
• at P21, mutant eyelashes are irregularly oriented and the surrounding fur is disorganized
• mutant eyelids are swollen and hypercellular and contain fewer irregularly spaced Meibomian gland orifices at the mucocutaneous junction
• the palpebral epidermis is thicker with 7-9 layers of keratinocytes relative to 2-3 in wild-type controls
• however, no major differences are observed in eyelid morphology at P5, P8 and P11
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• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age
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• at P21, mutant Meibomian glands exhibit disorganized, variably sized acini
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• a Meibomian gland bud is noted at P6 suggesting timely induction, but appears disorganized; this feature becomes more prominent at P11 and P21
• at P21, the swollen eyelids are hypercellular and contain severely malformed Meibomian glands with disorganized acini
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• while wild-type eyelids open at P12, mutant eyelids remain closed as late as P21
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• small palpebral fissure at P21
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• at P21, mutants display a >2-fold increase in epithelial cell proliferation in the eyelids, cornea, and conjunctiva, as determined by Ki67 staining
• Ki67-positive cells are significantly increased in mutant palpebral epidermis and eyelid hair follicles
• while Ki67-positive cells are restricted to basal epithelia in wild-type controls, they are also found in the spinous cell layers in the mutant cornea and conjunctiva
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• at 8 weeks of age, mutant lacrimal glands display excessive vasculature and disrupted acinar organization, unlike wild-type controls
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• at 8 weeks of age, mutant lacrimal glands display interspersed dark spots resembling necrotic spots
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• at P21 and at 10 weeks, the mutant conjunctival epithelium appears rough and discontinuous, indicating a disrupted epithelial barrier
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• at P21 and at 10 weeks, conjunctiva goblet cells are absent, unlike in wild-type controls
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• at P21, the mutant palpebral conjunctiva is swollen and inflamed (reddish)
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• at P21 and at 10 weeks, the mutant corneal epithelial basement membrane is thin and discontinuous, unlike in wild-type controls
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• at 8 weeks of age, mutant lacrimal glands display interspersed dark spots resembling necrotic spots
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• at P21, mutants display a >2-fold increase in epithelial cell proliferation in the eyelids, cornea, and conjunctiva, as determined by Ki67 staining
• Ki67-positive cells are significantly increased in mutant palpebral epidermis and eyelid hair follicles
• while Ki67-positive cells are restricted to basal epithelia in wild-type controls, they are also found in the spinous cell layers in the mutant cornea and conjunctiva
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• at P21, mutant Meibomian glands exhibit disorganized, variably sized acini
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• a Meibomian gland bud is noted at P6 suggesting timely induction, but appears disorganized; this feature becomes more prominent at P11 and P21
• at P21, the swollen eyelids are hypercellular and contain severely malformed Meibomian glands with disorganized acini
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• at P21, mutant sebaceous glands are significantly enlarged
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• at 8 weeks of age, mutant lacrimal glands display excessive vasculature and disrupted acinar organization, unlike wild-type controls
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• at 8 weeks of age, mutant lacrimal glands display interspersed dark spots resembling necrotic spots
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• at P21, an uneven lipid accumulation is noted in the Meibomian gland ducts
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• at 8 weeks of age, mutant lacrimal glands display numerous infiltrating cells, indicating inflammation
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• at 8 weeks of age, mutant lacrimal glands display numerous infiltrating cells, indicating inflammation
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• at P21, mutant Meibomian glands exhibit disorganized, variably sized acini
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• a Meibomian gland bud is noted at P6 suggesting timely induction, but appears disorganized; this feature becomes more prominent at P11 and P21
• at P21, the swollen eyelids are hypercellular and contain severely malformed Meibomian glands with disorganized acini
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• at P21, mutant sebaceous glands are significantly enlarged
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• at P21, an uneven lipid accumulation is noted in the Meibomian gland ducts
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• at P21, mutant eyelids contain significantly enlarged hair follicles
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• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age
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• at 8 weeks of age, a thicker extra-ocular muscle is observed
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• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age
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• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mutant pups die 3 - 6 days after birth with an overt diabetic phenotype
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• very few alpha cells are seen
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• the number of insulin-expressing cells is decreased
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• 2 - 6 days after birth mutant pups develop severe growth retardation
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• 2 - 6 days after birth mutant pups develop hyperglycemia
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• 2 - 6 days after birth mutant pups develop hypoinsulinemia with insulin levels in the pancrease at 18% of normal on P1 and 6% of normal on P3
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• at P3 ketones are seen in all mutants with glucose levels above 20mM
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5, the cornea and lens are not separated
• at E12.5, the neural crest cells migrate into the vitreous cavity and push the lens toward the cornea while in wild-type mice, the lens vesicle and surface ectoderm are completely separated
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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 04/23/2024 MGI 6.23 |
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