Analysis Tools
mortality/aging
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• 3.9% of mice are inviable at E14.5; however, no lethality is noted at E12.5
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skeleton
| N |
• despite reduced cartilage, chondrocyte proliferation is normal
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• adult mice with low amount of chondroitin sulfate (CS) exhibit general skeletal dysplasia including abnormal craniofacial growth, malocclusion and curvature of the spine
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• in mice with malocclusion, dysraphism of cranial suture is already evident at 4 weeks of age
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• at P28, mice exhibit contraction of the cranial base; the cranial base synchondrosis is deformed
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• at P0, mRNA expression level of beta-catenin in the periosteum and dermis of the calvarial region is significantly lower than in wild-type mice
• at P0, collagen fibers appear irregular, thick and aggregated in the calvaria
• at P28, mice exhibit higher and broader calvaria than wild-type controls
• at 25 weeks of age, the calvaria are significantly thinner in mice with malocclusion
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malocclusion
(
J:269621
)
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• at 25 weeks of age, surviving mice exhibit a malocclusion with angle class III
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• in mice with malocclusion, thinning of the mandible is already evident at 4 weeks of age
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• in mice with malocclusion, a thin palatal process of the maxilla with few osteoblast-lineage cells is already evident at 4 weeks of age
• at 25 weeks of age, the palatal process of maxilla is significantly thinner in mice with malocclusion
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short femur
(
J:166870
)
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• cartilage is not enriched in chondroitin sulfate unlike in wild-type mice
• type 2 collagen fibers aggregate abnormally in the resting and proliferating layers of the cartilage compared to in wild-type mice
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• deformation of the spheno-occipitalis synchondrosis begins at or before P7
• chondrocytes that stain immunopositive for aggrecan and collagen II appear disarranged while immunoreactivity of Wnt3a and beta-catenin is weak in the chondro-osseous junction
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• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
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• at E18.5 and 4 weeks after birth
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• at E18.5 and 4 weeks after birth
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• at P7, chondrocytes that stain immunopositive for aggrecan and collagen II appear disarranged while immunopositive intensities of Wnt3a and beta-catenin in the subchondral bone of spheno-occipitalis are weak
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• intramembranous ossification in the skull is impaired
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• at P0, ossification of the craniofacial region including palate, calvaria and cranial base is delayed
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• at P0, ossification of the cranial base is delayed
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• at P0, ossification of calvarial bones is delayed: collagen type 1-positive connective tissues covering bone surface are thin while immunoreactivity of Wnt3a and beta-catenin in the mesenchymal tissues surrounding the OPN-positive bones is attenuated
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joint laxity
(
J:269621
)
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• at 2 weeks of age, mice with malocclusion exhibit joint laxity
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growth/size/body
malocclusion
(
J:269621
)
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• at 25 weeks of age, surviving mice exhibit a malocclusion with angle class III
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short face
(
J:269621
)
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• at P28, face is shorter than in wild-type controls
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• 4.2% of P0 pups exhibit facial cleft including cleft lip
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• at P0, mean palate thickness is significantly less than that in wild-type mice
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• in mice with malocclusion, a thin palatal process of the maxilla with few osteoblast-lineage cells is already evident at 4 weeks of age
• at 25 weeks of age, the palatal process of maxilla is significantly thinner in mice with malocclusion
|
|
• at P0, palate ossification is delayed: connective tissue surrounding osteopontin (OPN) and collagen type 1-positive neonatal bones is thinner while immunostaining intensity of chondroitin sulfate (CS), Wnt3a and beta-catenin is reduced in the palatal mesenchyme at the osteogenic front
• mRNA expression of collagen type 1 and Mmp13 is significantly downregulated in the palate
• at 25 weeks of age, immunopositivity of Wnt3a and FGF2 is reduced in the mesenchymal tissue of palatal mucosa while immunostaining intensity of collagen type 1 is weak in the lamina propria of the palate in mice with malocclusion
• however, the cell proliferation rate of mesenchymal cells in the palatal regions is normal at E18
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cleft palate
(
J:269621
)
|
• at E18.5, ~5% of surviving embryos show cleft palate
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• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
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• in mice with malocclusion, an asymmetric aspect of the nasal cavity is already evident at 4 weeks of age
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• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
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facial cleft
(
J:269621
)
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• 4.2% of P0 pups exhibit facial cleft including cleft lip
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round head
(
J:269621
)
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• at P28, ~91% of mice exhibit a rounded skull shape, in the absence of severe skeletal anomalies
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• at P0, collagen fibers appear irregular, thick and aggregated in the dermis of the scalp
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• mice with malocclusion exhibit a small body size, already evident at 4 weeks of age
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• slightly
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• homozygotes derived from homozygous matings exhibit a lower growth rate than wild-type controls until weaning age (49.3% vs 70.5%, respectively)
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craniofacial
| N |
• skull circumference is normal
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• at P28, centroid size (used as the measure of craniofacial size) is significantly smaller than in wild-type mice
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• in mice with malocclusion, dysraphism of cranial suture is already evident at 4 weeks of age
|
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• at P28, mice exhibit contraction of the cranial base; the cranial base synchondrosis is deformed
|
|
• deformation of the spheno-occipitalis synchondrosis begins at or before P7
• chondrocytes that stain immunopositive for aggrecan and collagen II appear disarranged while immunoreactivity of Wnt3a and beta-catenin is weak in the chondro-osseous junction
|
|
• at P0, mRNA expression level of beta-catenin in the periosteum and dermis of the calvarial region is significantly lower than in wild-type mice
• at P0, collagen fibers appear irregular, thick and aggregated in the calvaria
• at P28, mice exhibit higher and broader calvaria than wild-type controls
• at 25 weeks of age, the calvaria are significantly thinner in mice with malocclusion
|
malocclusion
(
J:269621
)
|
• at 25 weeks of age, surviving mice exhibit a malocclusion with angle class III
|
|
• in mice with malocclusion, thinning of the mandible is already evident at 4 weeks of age
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• at E18.5, ~5% of surviving embryos exhibit severe developmental defects of the craniofacial region, including eye defects, cranial deformation and vascular malformation
• pups without cleft palate and lip can survive after birth; however, 8.1% of them exhibit severe craniofacial malformation after 4 weeks of age
• in mice with malocclusion, a curved frontonasal region, dysraphism of cranial suture and thinning of the cranium and mandible is already observed at 4 weeks of age
• at 25 weeks of age, mice with malocclusion show asymmetrical aspects in the frontal section
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short face
(
J:269621
)
|
• at P28, face is shorter than in wild-type controls
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• 4.2% of P0 pups exhibit facial cleft including cleft lip
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• at P0, mean palate thickness is significantly less than that in wild-type mice
|
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• in mice with malocclusion, a thin palatal process of the maxilla with few osteoblast-lineage cells is already evident at 4 weeks of age
• at 25 weeks of age, the palatal process of maxilla is significantly thinner in mice with malocclusion
|
|
• at P0, palate ossification is delayed: connective tissue surrounding osteopontin (OPN) and collagen type 1-positive neonatal bones is thinner while immunostaining intensity of chondroitin sulfate (CS), Wnt3a and beta-catenin is reduced in the palatal mesenchyme at the osteogenic front
• mRNA expression of collagen type 1 and Mmp13 is significantly downregulated in the palate
• at 25 weeks of age, immunopositivity of Wnt3a and FGF2 is reduced in the mesenchymal tissue of palatal mucosa while immunostaining intensity of collagen type 1 is weak in the lamina propria of the palate in mice with malocclusion
• however, the cell proliferation rate of mesenchymal cells in the palatal regions is normal at E18
|
cleft palate
(
J:269621
)
|
• at E18.5, ~5% of surviving embryos show cleft palate
|
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• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
|
|
• in mice with malocclusion, an asymmetric aspect of the nasal cavity is already evident at 4 weeks of age
|
|
• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
|
facial cleft
(
J:269621
)
|
• 4.2% of P0 pups exhibit facial cleft including cleft lip
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round head
(
J:269621
)
|
• at P28, ~91% of mice exhibit a rounded skull shape, in the absence of severe skeletal anomalies
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homeostasis/metabolism
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• at P0, pups with severe malformations exhibit a significantly lower amount of chondroitin sulfate (CS) chains than pups without severe abnormalities or wild-type control mice
• at 25 weeks of age, the amount of CS is significantly lower in all tissues of mice with malocclusion (skin, muscle/tendon, and bone/joint) than in mice without malocclusion or wild-type control mice
• total amount of CS chains is significantly lower in mice with severe abnormalities (malocclusion, skeletal dysplasia and facial cleft) than in mice without severe abnormalities
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limbs/digits/tail
short femur
(
J:166870
)
short limbs
(
J:166870
)
|
• at 25 weeks of age, mRNA expression of collagen type 1 is significantly downregulated in tail tissues of mice with severe abnormalities (malocclusion, skeletal dysplasia and facial cleft)
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integument
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• at 1 year of age, some aged mice with or without malformations exhibit focal alopecia
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• at 20 weeks of age, collagen fibers of the dermis appear disordered and aggregated
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• during routine handling, the back skin of aged mice shows hyperextensibility
• however, the thickness of dermis of the back skin is normal
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skin atrophy
(
J:269621
)
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• at 1 year of age, some aged mice with or without malformations exhibit atrophic skin
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vision/eye
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• at 25 weeks of age, mice with malocclusion exhibit abnormal eyes
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• at 25 weeks of age, collagen fibers of the cornea appear disordered and aggregated
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anophthalmia
(
J:269621
)
|
• at 25 weeks of age, the unilateral eyeball is missing in mice with severe malformations
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immune system
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• at 25 weeks of age, mice with malocclusion exhibit severe periodontitis
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respiratory system
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• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
|
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• in mice with malocclusion, an asymmetric aspect of the nasal cavity is already evident at 4 weeks of age
|
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• at E18.5, ~5% of surviving embryos show hypoplasia of the nasal cartilage with nasal septum deficiency and cleft palate
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reproductive system
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• homozygous matings yield a lower litter size (4.2 pups per litter) than wild-type or heterozygous matings (6.8 and 6.5 pups per litter, respectively)
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digestive/alimentary system
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• at P0, mean palate thickness is significantly less than that in wild-type mice
|
|
• in mice with malocclusion, a thin palatal process of the maxilla with few osteoblast-lineage cells is already evident at 4 weeks of age
• at 25 weeks of age, the palatal process of maxilla is significantly thinner in mice with malocclusion
|
|
• at P0, palate ossification is delayed: connective tissue surrounding osteopontin (OPN) and collagen type 1-positive neonatal bones is thinner while immunostaining intensity of chondroitin sulfate (CS), Wnt3a and beta-catenin is reduced in the palatal mesenchyme at the osteogenic front
• mRNA expression of collagen type 1 and Mmp13 is significantly downregulated in the palate
• at 25 weeks of age, immunopositivity of Wnt3a and FGF2 is reduced in the mesenchymal tissue of palatal mucosa while immunostaining intensity of collagen type 1 is weak in the lamina propria of the palate in mice with malocclusion
• however, the cell proliferation rate of mesenchymal cells in the palatal regions is normal at E18
|
cleft palate
(
J:269621
)
|
• at E18.5, ~5% of surviving embryos show cleft palate
|
