Analysis Tools
mortality/aging
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• at embryonic day 11.5 only one quarter to one third of embryos from wild-type x heterozygous matings are mutant
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• Background Sensitivity: smaller litter size likely due to in utero death on the C57BLKS background compared with a mixed background of AKR and C57BLKS
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pigmentation
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• white feet
(J:28035)
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• white belly spot
(J:13703)
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vision/eye
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• direct pupilary light response is weak or absent in approximately 60% of heterozygotes with a third of these having a bilateral deficit and the remainder only a unilateral deficit
• detectable as soon as the eyelids open
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• variable expressivity in the optic nerve phenotype such that heterozygotes can have optic nerves that are normal, small or missing on one side, or completely absent from both sides
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• 23 of 28 heterozygotes with diminished pupillary light response lack an optic nerve
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• optic nerve colobomas range from mild loss of nerve fibers on the surface of the optic cup to complete absence of the nerve and severe abnormalities of the peripapillary nerual retina, retinal pigment epithelium, and choroid
(J:60921)
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• variable unilateral or bilateral atrophy of the optic nerves
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• the optic nerves associated with reduced pupullary light response are smaller than normal, have degenerating fibers, and fewer ganglion cell axons than normal. Despite this, the ipsilateral population of ganglion cells is overrepresented in affected heterozygotes
• the optic nerves in heterozygotes with normal pupillary light response have fewer axons on average than those of wild-type controls
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• anterior and posterior subcapsular and cortical cataracts are present in a minority of affected heterozygotes
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• at birth affected heterozygotes have abnormal neural retina, buckled in severe cases, the optic nerves are smaller than normal and contain fewer axons, and the ganglion cell layer is thinner, with an increase in the number of dying cells
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• beginning at embryonic day 10.5 and persisting through embryonic day 13.5 the optic cup is 60 um more shallow than that of wild-type siblings
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• at embryonic day 12 the development of the optic fissure is delayed
(J:43133)
• delay in the closure of the optic fissure, with less than half of the heterozygous retinas being fused by embryonic day 13.5 when this process is completed in wild-type siblings
(J:53381)
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• large hyaloid vessels are present at up to 22 months of age and come from the optic nerve, not the sensory retina
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• at embryonic day 10.5 approximately 25% of heterozygotes have size disparities between the eyes
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• incomplete expressivity in abnormalities of the retinal morphology leaves some heterozygous adults with normal retinas and the severely affected having distorted organization of the neural retina, particularly the optic disc area, with the inner and outer nuclear layers distorted into folds, rosettes, or colobomas
(J:43133)
• after 7 months of age retinal detachment, subretinal macrophages, and subretinal neovascularization are found
(J:60921)
• retinal folds and small patches of retinal thinning are common and in 21% of affected heterozygotes small patches of retinal dysplasia are found close to the optic nerve or in the peripheral retina
(J:60921)
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• subretinal neovascularization with submacular hemorrhage and fibrosis is found and accompanies most instances of retinal degeneration in these heterozygotes
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• beginning at embryonic day 11.5 there is a sparsely cellularized layer formed on the vitreal surface of the dorsal retina
• although the proliferation index is normal and cell death in the neuroal retina is normal, BrdU labeling of embyronic day 10.5 shows that there is a delay in exit from the cell cycle in cells of the developing retina
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• at embryonic day 12 the layers of the retina are often disrupted
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• in the most severely affected heterozygous adults the ganglion cell layer has few cells and these may not be ganglion cells
(J:43133)
• an increase in ectopic ipsilaterally projecting ganglion cells, outside of the ventrotemporal part of the retina, is found in heterozygotes with a small optic nerve
(J:43133)
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• in the most severely affected heterozygotes
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• reduced in thickness
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• in some P0 retinas, the neural retina is buckled, resulting in detachment from the pigment epithelium
(J:43133)
• localized, posterior pole, nonrhegmatogenous retinal detachment is found and is usually temporal to the optic nerve
(J:60921)
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• in severely affected mice, the inner and outer nuclear layers distorted into folds
(J:43133)
• retinal folds are common
(J:60921)
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• surface area of the retina is 10% snmaller, on average, in affected heterozygotes
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growth/size/body
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• at embryonic day 9.5 approximately one third of the embryos from wild-type x heterozygous matings are visiblyh smaller than normal
• at embryonic day 10.5 approximately 60% of embryos from wild-type x heterozygous matings are normal size and the remainder are either small, defined as <4mm crown to rump length, or diminutive, defined as <3.5mm crown to rump length, with most of the cells in the diminutive embryos being apoptotic according to TUNEL staining
• at embryonic day 11.5 short tailed embryos are 5.9mm instead of the wild-type 6.3mm
• at embryonic day 12.5 short tailed embryos are 8.1mm instead of the wild-type 8.9mm
• at embryonic day 13.5 short tailed embryos are 9.8mm instead of the wild-type 10.6mm
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• mutants are 20% smaller than wild-type littermates and this persists into adulthood
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limbs/digits/tail
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• triphalangeal first digit and and extra preaxial digit are often found
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• polydactyly affecting one to three feet
(J:13703)
• first seen at embryonic day 13.5, principally on the right rear paw
(J:53381)
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• mutants can have fused or wedge-shaped hemivertebrae at the sites of tail kinks
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• mutants have fewer caudal vertebrae
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• kinks found as early as embryonic day 12.5
(J:53381)
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skeleton
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• mutants can have fused or wedge-shaped hemivertebrae at the sites of tail kinks
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• mutants have fewer caudal vertebrae
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• mutants have six lumbar vertebrae instead of the wild-type five
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nervous system
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• in approximately 30% of heterozygotes
(J:43133)
• found by embronic day 11.5
(J:53381)
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• variable expressivity in the optic nerve phenotype such that heterozygotes can have optic nerves that are normal, small or missing on one side, or completely absent from both sides
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• 23 of 28 heterozygotes with diminished pupillary light response lack an optic nerve
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• optic nerve colobomas range from mild loss of nerve fibers on the surface of the optic cup to complete absence of the nerve and severe abnormalities of the peripapillary nerual retina, retinal pigment epithelium, and choroid
(J:60921)
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• variable unilateral or bilateral atrophy of the optic nerves
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• the optic nerves associated with reduced pupullary light response are smaller than normal, have degenerating fibers, and fewer ganglion cell axons than normal. Despite this, the ipsilateral population of ganglion cells is overrepresented in affected heterozygotes
• the optic nerves in heterozygotes with normal pupillary light response have fewer axons on average than those of wild-type controls
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behavior/neurological
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• direct pupilary light response is weak or absent in approximately 60% of heterozygotes with a third of these having a bilateral deficit and the remainder only a unilateral deficit
• detectable as soon as the eyelids open
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cellular
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• pulse labeling shows impaired ribosome biogenesis, particularly of the 28S rRNA
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• embryonic fibroblast cultures have a slower doubling time, decreased ratio of G1 to S phase, and an increased length of G1 after serum stimulation
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cardiovascular system
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• subretinal neovascularization with submacular hemorrhage and fibrosis is found and accompanies most instances of retinal degeneration in these heterozygotes
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embryo
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• at embryonic day 9.5 approximately one third of the embryos from wild-type x heterozygous matings are visiblyh smaller than normal
• at embryonic day 10.5 approximately 60% of embryos from wild-type x heterozygous matings are normal size and the remainder are either small, defined as <4mm crown to rump length, or diminutive, defined as <3.5mm crown to rump length, with most of the cells in the diminutive embryos being apoptotic according to TUNEL staining
• at embryonic day 11.5 short tailed embryos are 5.9mm instead of the wild-type 6.3mm
• at embryonic day 12.5 short tailed embryos are 8.1mm instead of the wild-type 8.9mm
• at embryonic day 13.5 short tailed embryos are 9.8mm instead of the wild-type 10.6mm
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integument
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• white feet
(J:28035)
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• white belly spot
(J:13703)
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| optic atrophy | DOID:5723 |
OMIM:PS165500 |
J:28035 | |
