Analysis Tools
mortality/aging
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• large subset of heterozygotes die postnatally
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cellular
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• formation of bone-like nodules by cultured calvarial osteoblasts (OBs) is reduced between 9 and 16 days in culture compared to wild-type cells; average area of individual nodules is reduced relative to controls
• nodular Alizarin red-binding capacity (staining for calcium in bone) is reduced 3.2 fold, indicative of decreased calcium deposition by osteoblasts
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• after induction of cytoprotective unfolded protein response in cultured calvarial OBs, apoptosis is elevated compared to controls, with a 10% relative increase in TUNEL-positive picnotic OBs at 16 days in culture
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growth/size/body
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• animals are smaller than wild-type littermates; at 9 weeks, all animals examined have 'slender' bodies relative to controls
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• at 16 weeks, average body mass is ~20 grams compared to wild-type body mass of ~32 grams
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• at 16 weeks, average body length is ~8.9 cm compared to ~10 cm in wild-type
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nervous system
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• intracranial hemorrhages are seen in subset of heterozygotes that die postnatally
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skeleton
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• formation of bone-like nodules by cultured calvarial osteoblasts (OBs) is reduced between 9 and 16 days in culture compared to wild-type cells; average area of individual nodules is reduced relative to controls
• nodular Alizarin red-binding capacity (staining for calcium in bone) is reduced 3.2 fold, indicative of decreased calcium deposition by osteoblasts
|
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• after induction of cytoprotective unfolded protein response in cultured calvarial OBs, apoptosis is elevated compared to controls, with a 10% relative increase in TUNEL-positive picnotic OBs at 16 days in culture
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• skeletal phenotype is detectable between 6 and 11 days after birth
• animals reaching adulthood display mildly to moderately dystrophic limbs
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• subset of heterozygotes that die postnatally show thin calvaria
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• femoral periosteum at 12 weeks displays greater caspase 3-immunoreactivity indicating an elevated basal level of apoptosis (~14% higher relative to controls); an increased number of TUNEL-positive cells is observed in periosteum also
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• at 21 weeks, mediolateral shaft diameter is ~1.45 mm, compared to ~1.88 in wild-type
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short femur
(
J:129569
)
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• at 21 weeks, femur length of heterzygotes is ~14.7 mm, compared to ~15.3 mm in wild-type
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• ~50% of animals have deformed fibulae at 16 weeks of age
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• at 16 weeks, all animals examined show pelvic girdle bone abnormalities including deteriorated ischium
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• at 16 weeks, all animals examined show pelvic girdle bone abnormalities including deteriorated pubis region
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• at 16 weeks, all animals examined show kyphoscoliosis
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• at 16 weeks, bone mineral content is ~309 mg compared to ~935 mg in wild-type animals
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• at 16 weeks, bone mineral density (without head) is 42 mg/cm2 compared to ~58 mg/cm2 in wild-type
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• cortical structure has less-parallel, less-densely packed network of collagen bundles compared to controls
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• cultured primary calvarial osteoblasts (OBs) show growth anomalies, with stimulated OBs displaying a limited saturation density
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• at 16 weeks, significant numbers of heterozygotes show a variety of bone fractures, including the tibia, humerus, ulna, and radius whereas no fractures are observed in wild-type
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limbs/digits/tail
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• femoral periosteum at 12 weeks displays greater caspase 3-immunoreactivity indicating an elevated basal level of apoptosis (~14% higher relative to controls); an increased number of TUNEL-positive cells is observed in periosteum also
|
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• at 21 weeks, mediolateral shaft diameter is ~1.45 mm, compared to ~1.88 in wild-type
|
short femur
(
J:129569
)
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• at 21 weeks, femur length of heterzygotes is ~14.7 mm, compared to ~15.3 mm in wild-type
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• ~50% of animals have deformed fibulae at 16 weeks of age
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craniofacial
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• subset of heterozygotes that die postnatally show thin calvaria
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homeostasis/metabolism
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• total alkaline phosphatase levels are significantly elevated compared to wild-type littermates at 16 weeks
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• mice have elevated calcitonin levels (pg/ml), compared to controls; elevation is more pronounced in female heterozygotes
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• mice have elevated parathyroid hormone (PTH) levels (pg/ml), compared to wild-type littermates
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reproductive system
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• female heterozygotes produce smaller litters as result of reduced body size
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cardiovascular system
hemorrhage
(
J:129569
)
|
• subset of heterozygotes that die postnatally show hemorrhaging at joint cavities
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• intracranial hemorrhages are seen in subset of heterozygotes that die postnatally
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adipose tissue
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• at 16 weeks, subcutaneous fat span is ~2.9 mm compared to ~5.1 mm in wild-type
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integument
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• dermis contains more heterogeneous populations of fibroblasts with smaller nuclei, aberrant dilated electron-dense endoplasmic reticula (ERs), lysosomes, and empty autophagic-like vacuoles interspersed throughout the cells
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteogenesis imperfecta type 2 | DOID:0110341 |
OMIM:166210 |
J:129569 | |
