Phenotypes Associated with This Genotype

Genotype
MGI:3045084

• Allelic Composition: Col1a1^tm1Jae/Col1a1^tm1Jae
• Genetic Background: involves: 129S4/SvJae * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

craniofacial

abnormal neurocranium morphology ( J:90884 )

• at >4 weeks of age, mutants showed increased bone deposition in calvariae mainly at the inner periosteal surface adjacent to the dura mater

• calvarial thickness nearly doubled by ~10 months of age

• homozygotes had normal circulating levels of PTH, but showed increased calcein labeling of calvarial surfaces

thick neurocranium ( J:90884 )

• calvarial thickness nearly doubled by ~10 months of age

growth/size/body

decreased body weight ( J:82606 )

• homozygotes showed a normal mean body weight throughout the 36-wk observation period, except for a 9.8% reduction at 18 wks

limbs/digits/tail

abnormal limb bone morphology ( J:53079 )

• adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone

skeleton

skeleton phenotype ( J:85591 )

N • homozygotes showed normal tooth eruption

increased osteoblast apoptosis ( J:90884 )

• beginning at about 2 weeks of age, homozygotes showed increased osteoblast apoptosis, despite increased bone deposition

increased osteocyte apoptosis ( J:90884 )

• beginning at about 2 weeks of age, homozygotes showed increased osteocyte apoptosis, despite increased bone deposition

abnormal osteoblast differentiation ( J:85591 , J:90884 )

• at 4 weeks, homozygotes showed an increase in tibial trabecular bone volume despite an overall decrease in osteoblast activity in trabecular bone (J:85591)

• in contrast, homozygotes displayed normal tibial cortical bone thickness, and a relatively normal tibial periosteal mineral apposition rate (J:85591)

• at greater 4 weeks of age, mutants began to show increased bone deposition of endosteal trabecular bone in tibial/femoral bones (J:90884)

abnormal neurocranium morphology ( J:90884 )

• at >4 weeks of age, mutants showed increased bone deposition in calvariae mainly at the inner periosteal surface adjacent to the dura mater

• calvarial thickness nearly doubled by ~10 months of age

• homozygotes had normal circulating levels of PTH, but showed increased calcein labeling of calvarial surfaces

thick neurocranium ( J:90884 )

• calvarial thickness nearly doubled by ~10 months of age

abnormal osteoclast physiology ( J:53079 )

• in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts

• the bone resorption area and the number of osteoclasts/mm2 were significantly increased (~5-fold) after PTH injection in wild-type, but not in homozygous mutant mice

• homozygotes were not resistant to other skeletal effects of PTH

• after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type

abnormal limb bone morphology ( J:53079 )

• adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone

abnormal osteocyte morphology ( J:90884 )

• at >2 weeks of age, homozygotes showed loss of osteocytes from their lacunae in the calvariae and in the shafts of long bones

abnormal osteocyte lacuna morphology ( J:90884 )

• the number of "empty" lacunae increased with age

osteopetrosis ( J:85591 )

• homozygotes exhibited a mild osteopetrotic phenotype, that is, a mild, but significant, increase in tibial trabecular number and volume, and a sharp decrease in trabecular separation

failure of bone resorption ( J:85591 )

• homozygotes showed impaired osteoclastic bone resorption in trabecular bone: namely, an increase in osteoclast number and surface in long bones

joint contracture ( J:53079 )

• adult homozygotes developed joint contractures

vision/eye

vision/eye phenotype ( J:82606 )

N • homozygotes showed no anterior segment defects: the angle was open, and the depth of the anterior chamber appeared normal

ocular hypertension ( J:82606 )

• homozygotes showed a significant increase in mean intraocular pressure at 18, 24, and 36 weeks (21%, 44%, and 36%, respectively)

• homozygotes displayed an increased accumulation of collagen I in conjunctiva, subconjunctival tissue, and sclera, suggesting an association between IOP regulation and fibrillar collagen turnover

immune system

abnormal osteoclast physiology ( J:53079 )

• in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts

• the bone resorption area and the number of osteoclasts/mm2 were significantly increased (~5-fold) after PTH injection in wild-type, but not in homozygous mutant mice

• homozygotes were not resistant to other skeletal effects of PTH

• after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type

cellular

increased osteoblast apoptosis ( J:90884 )

• beginning at about 2 weeks of age, homozygotes showed increased osteoblast apoptosis, despite increased bone deposition

increased osteocyte apoptosis ( J:90884 )

• beginning at about 2 weeks of age, homozygotes showed increased osteocyte apoptosis, despite increased bone deposition

abnormal osteoblast differentiation ( J:85591 , J:90884 )

• at 4 weeks, homozygotes showed an increase in tibial trabecular bone volume despite an overall decrease in osteoblast activity in trabecular bone (J:85591)

• in contrast, homozygotes displayed normal tibial cortical bone thickness, and a relatively normal tibial periosteal mineral apposition rate (J:85591)

• at greater 4 weeks of age, mutants began to show increased bone deposition of endosteal trabecular bone in tibial/femoral bones (J:90884)

hematopoietic system

abnormal osteoclast physiology ( J:53079 )

• in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts

• the bone resorption area and the number of osteoclasts/mm2 were significantly increased (~5-fold) after PTH injection in wild-type, but not in homozygous mutant mice

• homozygotes were not resistant to other skeletal effects of PTH

• after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type