cellular
• decrease in chondrocyte proliferation at E14.5
|
growth/size/body
short snout
(
J:57297
)
• at birth, homozygotes show a foreshortened snout
|
• at birth, homozygotes are consistently shorter than wild-type mice
|
• at birth mutants display severe short-limb dwarfism
|
skeleton
• decrease in chondrocyte proliferation at E14.5
|
• 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
|
• at 18.5 dpc, some of the wrist bones of homozygotes appear partly fused
|
• 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)
|
• 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
|
• at birth, mutant long bones are one-third the length of wild-type long bones
|
short humerus
(
J:73071
)
short ulna
(
J:73071
)
short fibula
(
J:73071
)
short tibia
(
J:73071
)
• growth retardation of tibia
|
short scapula
(
J:73071
)
• length of scapula is shorter
|
• at birth, homozygotes display a foreshortened mandible
|
domed cranium
(
J:57297
)
• at birth, homozygotes show a rounded skull
|
• mutant ribs do not display excessive calcification
|
short ribs
(
J:57297
)
• homozygotes have significantly shortened ribs
|
• 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)
|
• 18.5 dpc, mutant humeri display no identifiable trabecular bone in the primary spongiosa
|
• at 18.5 dpc, homozygotes show abnormal joint formation
|
• skeletal growth retardation
|
• 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
|
• 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
|
• 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
|
• 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)
|
• reduced chondrocyte proliferation and severe short-limb dwarfism are seen
|
• in homozygotes, appendicular skeletal elements fail to ossify
|
• 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
|
• homozygotes exhibit absence of endochondral bone formation prior to birth
• in homozygous newborns, most endochondral bones are shorter and relatively malformed
|
limbs/digits/tail
• at 18.5 dpc, some of the wrist bones of homozygotes appear partly fused
|
• 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)
|
• 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
|
• 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)
|
• at 13.5 dpc, homozygotes display visibly shortened forelimbs
|
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)
|
mortality/aging
• homozygotes that develop to term die at birth due to respiratory failure
|
• 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
|
craniofacial
• at birth, homozygotes display a foreshortened mandible
|
domed cranium
(
J:57297
)
• at birth, homozygotes show a rounded skull
|
short snout
(
J:57297
)
• at birth, homozygotes show a foreshortened snout
|
respiratory system