Analysis Tools
cellular
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• decrease in chondrocyte proliferation at E14.5
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growth/size/body
short snout
(
J:57297
)
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• at birth, homozygotes show a foreshortened snout
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• at birth, homozygotes are consistently shorter than wild-type mice
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• at birth mutants display severe short-limb dwarfism
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skeleton
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• decrease in chondrocyte proliferation at E14.5
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• in homozygotes, most skeletal elements are present in the right position and in the right number; however, all elements of the axial and appendicular skeletons exhibit dwarfism
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• at 18.5 dpc, some of the wrist bones of homozygotes appear partly fused
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• mutant long bones fail to show any signs of calcification at 14.5 dpc, as expected; instead, calcification is first noted at 16.5 dpc in mutant scapula and humerus, and slightly later in radius and ulna
(J:57297)
• depletion of non-mineralized cartilage at articular ends of long bones
(J:73071)
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• at 18.5 dpc, the mutant humerus and ulna remain partly fused
• at 18.5 dpc, mutant humeri display no identifiable cortical bone, even in vascularized areas of the perichondrium
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• at birth, mutant long bones are one-third the length of wild-type long bones
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short humerus
(
J:73071
)
short ulna
(
J:73071
)
short fibula
(
J:73071
)
short tibia
(
J:73071
)
|
• growth retardation of tibia
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short scapula
(
J:73071
)
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• length of scapula is shorter
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• at birth, homozygotes display a foreshortened mandible
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domed cranium
(
J:57297
)
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• at birth, homozygotes show a rounded skull
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• mutant ribs do not display excessive calcification
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short ribs
(
J:57297
)
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• homozygotes have significantly shortened ribs
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• at 18.5 dpc, homozygotes show no osteocalcin expression in endochondral bones of the appendicular or axial skeleton, indicating absence of mature osteoblasts in mutant long bones
• in contrast, mature osteoblasts are present in mutant bones formed by intramembranous ossification (e.g. flat bones of the skull, mandible, and clavicle)
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• 18.5 dpc, mutant humeri display no identifiable trabecular bone in the primary spongiosa
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• at 18.5 dpc, homozygotes show abnormal joint formation
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• skeletal growth retardation
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• although initial cartilage elements develop normally, 13.5-dpc mutant forelimbs show a slight reduction in each cartilage element relative to wild-type; this size difference is clearly visible at 14.5 dpc
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• as early as 12.5 dpc, mutant humeri show a ~50% reduction in chondrocyte proliferation; in addition, the length of proliferative zone is severely reduced
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• at 13.5 dpc, mutant humeri show absence of typical hypertrophic chondrocytes
• at 14.5 dpc, some hypertrophic cells are found in the center of mutant humeri but are neither as large nor as well-organized as those of wild-type bones
• such hypertrophic cells are surrounded by less mature chondrocytes and show no signs of vascularization or cortical bone formation
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• homozygotes display ectopic maturation of chondrocytes: chondrocyte differentiation is initially delayed, but when it occurs, hypertrophic cells fail to exhibit a stacked columnar organization and occupy inappropriate positions close to articular surfaces
(J:57297)
• premature chondrocyte hypertrophy, resulting in depletion of non-mineralized cartilage at articular ends of long bones
(J:73071)
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• reduced chondrocyte proliferation and severe short-limb dwarfism are seen
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• in homozygotes, appendicular skeletal elements fail to ossify
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• at 16.5 dpc, mutant humeri show ectopic initial calcification in the center of cartilage only, suggesting that mineralization occurs in cartilage and not in association with a bone collar
• by 18.5 dpc, ectopic calcification extends closer to the articular surfaces in mutant bones, including the humerus, sternum, vertebrae, and cartilaginous synchondroses of the base of the skull
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• homozygotes exhibit absence of endochondral bone formation prior to birth
• in homozygous newborns, most endochondral bones are shorter and relatively malformed
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limbs/digits/tail
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• at 18.5 dpc, some of the wrist bones of homozygotes appear partly fused
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• homozygotes display failure of digit segmentation: at 18.5 dpc, mutant digits remain unsegmented and uncalcified
(J:57297)
• failure of digit segmentation and ossification
(J:73071)
|
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• at 18.5 dpc, the mutant humerus and ulna remain partly fused
• at 18.5 dpc, mutant humeri display no identifiable cortical bone, even in vascularized areas of the perichondrium
|
short humerus
(
J:73071
)
short ulna
(
J:73071
)
short fibula
(
J:73071
)
short tibia
(
J:73071
)
|
• growth retardation of tibia
|
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• at birth, homozygotes display significant dwarfism of the limbs
(J:57297)
• 60-80% reduction in the length of the stylopod and the zeugopod at birth
(J:73071)
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• at 13.5 dpc, homozygotes display visibly shortened forelimbs
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short tail
(
J:57297
)
vision/eye
| N |
• no rosettes are observed in the retina
(J:78708)
• astrocyte precursor cells at the optic disc and in the optic nerve develop normally
(J:83530)
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mortality/aging
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• homozygotes that develop to term die at birth due to respiratory failure
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• about 50% of homozygotes die at midgestation between 10.5 and 12.5 dpc, probably as a result of circulatory defects
• some lethality also occurs at later stages of gestation
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craniofacial
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• at birth, homozygotes display a foreshortened mandible
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domed cranium
(
J:57297
)
|
• at birth, homozygotes show a rounded skull
|
short snout
(
J:57297
)
|
• at birth, homozygotes show a foreshortened snout
|
respiratory system
