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Allele Symbol Allele Name Allele ID |
Col1a1M1Jrt mutation 1, Janet Rossant MGI:5620941 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• low bone mineral density
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• high incidence of bone fractures in affected mice
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• some affected mice show difficulty walking
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• myocardial hypertrophy detected upon necropsy at 20-25 weeks of age
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• dentin is abnormally mineralized
• no evidence of malocclusion or dentinogenesis imperfecta
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• although born phenotypically normal, by 3 weeks of age, both male and female mice are visibly smaller than wild-type controls
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• significant reduction in body weight evident at 3 weeks and throughout life
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• by 3 weeks of age, both male and female mice are leaner than wild-type controls
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• flaccid tails by 3 weeks of age
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• by 8 weeks of age, some mice begin to show a wobbly and uneven gait that becomes more pronounced with age
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• dentin is abnormally mineralized
• no evidence of malocclusion or dentinogenesis imperfecta
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• degenerative joint disease detected upon necropsy at 20-25 weeks of age
• early onset osteoarthritis
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• normal femoral cortical thickness but significantly decreased femoral cross-sectional area and polar moment of inertia
• destructive 3-point bending of femurs revealed significantly weaker, less tough, less stiff, and more brittle bones, with a 39% decrease in strength, a 89% decrease in toughness and a 77% decrease in failure strain but no significant change in the elastic modulus
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• tendon collagen fibrils are significantly smaller in diameter
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• tendon teased out from the tail is more frayed than normal
• tendon is easily torn during normal dissection
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• at 8 weeks of age, 48% of male and 28% of female mice display noticeable curvature of the spine in X-ray images
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• bone collagen fibrils are significantly smaller in diameter
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• at all ages tested
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• at all ages tested
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• decreased trabecular bone volume/tissue volume (Tb. BV/TV) in both femoral and vertebral (lumbar vertebrae) bones
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• drastic reduction in mechanical and material properties in cortical bone, as assessed by 3-point bending of femurs
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• significantly increased osteoblast surface at 8 weeks of age
• osteoblasts show distended endoplasmic reticulum, suggesting that abnormal collagen chains accumulate intracellularly
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• significantly increased osteoblast number at 8 weeks of age
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• in the femoral metaphysis, low Tb. BV/TV is associated with an increase in trabecular separation and a decrease in trabecular number but not in trabecular thickness
• in lumbar vertebrae, low BV/TV is associated with a decrease in trabecular separation, trabecular number, and trabecular thickness
• higher structure model index (SMI), indicating decreased structural quality, at both bone sites
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• in both femoral and vertebral (lumbar vertebrae) bones
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• only in lumbar vertebrae
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• only in the femoral metaphysis
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• only in lumbar vertebrae
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• in trabecular bone, calcein labels, where present, are generally diffuse, suggesting impaired and disorganized mineralization
• in vitro, the total number of mesenchymal progenitors (CFU-F) and osteoprogenitors (CFU-ALP) is normal, but the number of mineralized osteoblast colonies (CFU-O) is significantly decreased in stromal cells from 5-wk-old but not 20-wk-old mice relative to wild-type controls
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• although osteoclast surface and number are not significantly altered at 8 weeks, serum from both 5-wk and 20-wk-old show higher concentrations of CTX-1, a marker of bone resorption, than that from wild-type controls
• in vitro, osteoclast number and size in spleen-derived cultures are normal
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• by 8 weeks of age
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• by 8 weeks of age, bones are soft and friable upon cutting
• multiple fractures evident in X-rays, with age- and bone-site related variation in the % of affected mice
• in young mice, most common fracture sites include the pelvis, olecranon process, and zygomatic arch, with frequencies of 82%, 80%, and 68% of mice, respectively
• the % of mice with fractured tarsals increases from 20% at 8 weeks to 58% at 20 weeks of age
• the % of mice with fractured scapulae and arthritic knees increases between 8 and 20 weeks of age (28% to 63% and 0% to 33% for scapulae and knees, respectively)
• significant number of mice with fractured tibial and fibular bones at 30 and 50 weeks of age
• however, no gross skeletal structural anomalies or detectable fractures at E18.5 or at birth
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• normal femoral cortical thickness but significantly decreased femoral cross-sectional area and polar moment of inertia
• destructive 3-point bending of femurs revealed significantly weaker, less tough, less stiff, and more brittle bones, with a 39% decrease in strength, a 89% decrease in toughness and a 77% decrease in failure strain but no significant change in the elastic modulus
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• myocardial hypertrophy detected upon necropsy at 20-25 weeks of age
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• tendon collagen fibrils are significantly smaller in diameter
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• tendon teased out from the tail is more frayed than normal
• tendon is easily torn during normal dissection
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• in vitro, collagen fibrils are significantly smaller in diameter in extracellular matrices deposited by dermal fibroblasts
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• skin is more easily torn but of normal thickness
• tensile tests suggested that skin has a lower failure strain, is less extensible with a lower failure displacement, and requires less energy to failure
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| N |
• normal plasma biochemical parameters, including concentrations of alkaline phosphatase, calcium, phosphorus, magnesium, cholesterol, triglycerides, glucose, and creatinine, at 16 weeks of age
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• total collagen content of extracellular matrices deposited in long-term cultures of dermal fibroblasts is ~40% that of wild-type controls
• type V and III collagens are not altered, but type I collagen in mutant matrices is reduced to only ~30% of that in wild-type cultures, such that the relative amounts of types V and III collagen to the total are increased, whereas that of type I collagen is decreased
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• dentin is abnormally mineralized
• no evidence of malocclusion or dentinogenesis imperfecta
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• myocardial hypertrophy detected upon necropsy at 20-25 weeks of age
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• degenerative joint disease detected upon necropsy at 20-25 weeks of age
• early onset osteoarthritis
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• significant reduction in percent body fat at 3 weeks and throughout life
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• extracellular matrices deposited in long-term cultures of dermal fibroblasts appear more fragile and are easily dislodged from the plate by physical disturbance
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• poor breeding success
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| N |
• normal hearing as indicated by clickbox hearing tests
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Ehlers-Danlos syndrome | DOID:13359 |
OMIM:PS130000 |
J:216423 | |
| osteogenesis imperfecta type 4 | DOID:0110340 |
OMIM:166220 |
J:216423 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit substantial limping
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• mice show decreased rearing attempts
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• mice travel less distance in the open field glass chamber compared to wild-type mice
• overall counts of rotations in a home cage running wheel for one hour are reduced
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• mice show decreased paw withdrawal thresholds to mechanical stimulation indicating increased sensitivity to mechanical stimuli
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• mice show decreased withdrawal latency to heat stimuli indicating increased heat sensitivity
• mice show increased behavioral responses to acetone indicating increased sensitivity to cold stimuli
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• improper healing of the femur at the hip joint
• hyperplastic callus formation of olecranon process
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• hindpaw bone deformities
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• deformity and fracture of olecranon processes
• hyperplastic callus formation of olecranon process
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• improper healing of the femur at the hip joint
• hyperplastic callus formation of olecranon process
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• deformity and fracture of olecranon processes
• hyperplastic callus formation of olecranon process
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• deformity of coxae
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• reduction in cervical intervertebral disc space
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• decrease in bone volume/tissue volume
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• decrease in cortical thickness
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• atlanto-occipital joint dislocation
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• deformity and fracture of olecranon processes
• tarsal-metatarsal fracture
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteogenesis imperfecta type 4 | DOID:0110340 |
OMIM:166220 |
J:228439 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/30/2024 MGI 6.23 |
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