growth/size/body region phenotype

• decreased body weight
  • homozygotes showed a normal mean body weight throughout the 36-wk observation period, except for a 9.8% reduction at 18 wks
  (MGI Ref ID J:82606)

hematopoietic system phenotype

• abnormal osteoclast physiology
  • after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type
  (MGI Ref ID J:53079)
  • homozygotes were not resistant to other skeletal effects of PTH
  (MGI Ref ID J:53079)
  • 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
  (MGI Ref ID J:53079)
  • in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts
  (MGI Ref ID J:53079)

immune system phenotype

• abnormal osteoclast physiology
  • after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type
  (MGI Ref ID J:53079)
  • homozygotes were not resistant to other skeletal effects of PTH
  (MGI Ref ID J:53079)
  • in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts
  (MGI Ref ID J:53079)
  • 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
  (MGI Ref ID J:53079)

limbs/digits/tail phenotype

• abnormal limb bone morphology
  • adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone
  (MGI Ref ID J:53079)

cellular phenotype

• abnormal osteoblast differentiation
  • at greater 4 weeks of age, mutants began to show increased bone deposition of endosteal trabecular bone in tibial/femoral bones
  (MGI Ref ID J:90884)
  • at 4 weeks, homozygotes showed an increase in tibial trabecular bone volume despite an overall decrease in osteoblast activity in trabecular bone
  (MGI Ref ID J:85591)
  • in contrast, homozygotes displayed normal tibial cortical bone thickness, and a relatively normal tibial periosteal mineral apposition rate
  (MGI Ref ID J:85591)

• increased osteoblast apoptosis
  • beginning at about 2 weeks of age, homozygotes showed increased osteoblast apoptosis, despite increased bone deposition
  (MGI Ref ID J:90884)

• increased osteocyte apoptosis
  • beginning at about 2 weeks of age, homozygotes showed increased osteocyte apoptosis, despite increased bone deposition
  (MGI Ref ID J:90884)

mammalian phenotype

• skeleton phenotype
  • Normal - homozygotes showed normal tooth eruption
  (MGI Ref ID J:85591)

• vision/eye phenotype
  • Normal - homozygotes showed no anterior segment defects: the angle was open, and the depth of the anterior chamber appeared normal
  (MGI Ref ID J:82606)

skeleton phenotype

• abnormal osteocyte morphology
  • at >2 weeks of age, homozygotes showed loss of osteocytes from their lacunae in the calvariae and in the shafts of long bones
  (MGI Ref ID J:90884)

• osteopetrosis
  • 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
  (MGI Ref ID J:85591)

• abnormal osteoblast differentiation
  • at 4 weeks, homozygotes showed an increase in tibial trabecular bone volume despite an overall decrease in osteoblast activity in trabecular bone
  (MGI Ref ID J:85591)
  • at greater 4 weeks of age, mutants began to show increased bone deposition of endosteal trabecular bone in tibial/femoral bones
  (MGI Ref ID J:90884)
  • in contrast, homozygotes displayed normal tibial cortical bone thickness, and a relatively normal tibial periosteal mineral apposition rate
  (MGI Ref ID J:85591)

• abnormal osteoclast physiology
  • after i.p. injection of PTH, calcemic responses were significantly lower in homozygotes versus wild-type
  (MGI Ref ID J:53079)
  • in contrast to wild-type, homozygotes showed resistance to PTH-induced bone resorption, with only a few resorption spaces and rare osteoclasts
  (MGI Ref ID J:53079)
  • 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
  (MGI Ref ID J:53079)
  • homozygotes were not resistant to other skeletal effects of PTH
  (MGI Ref ID J:53079)

• abnormal osteocyte lacuna morphology
  • the number of "empty" lacunae increased with age
  (MGI Ref ID J:90884)

• increased osteoblast apoptosis
  • beginning at about 2 weeks of age, homozygotes showed increased osteoblast apoptosis, despite increased bone deposition
  (MGI Ref ID J:90884)

• failure of bone resorption
  • homozygotes showed impaired osteoclastic bone resorption in trabecular bone: namely, an increase in osteoclast number and surface in long bones
  (MGI Ref ID J:85591)

• abnormal limb bone morphology
  • adult homozygotes showed bony deformities, particularly of long bones, with increased deposition of woven bone
  (MGI Ref ID J:53079)

• thick neurocranium
  • calvarial thickness nearly doubled by ~10 months of age
  (MGI Ref ID J:90884)

• abnormal neurocranium morphology
  • at >4 weeks of age, mutants showed increased bone deposition in calvariae mainly at the inner periosteal surface adjacent to the dura mater
  (MGI Ref ID J:90884)
  • homozygotes had normal circulating levels of PTH, but showed increased calcein labeling of calvarial surfaces
  (MGI Ref ID J:90884)
  • calvarial thickness nearly doubled by ~10 months of age
  (MGI Ref ID J:90884)

• increased osteocyte apoptosis
  • beginning at about 2 weeks of age, homozygotes showed increased osteocyte apoptosis, despite increased bone deposition
  (MGI Ref ID J:90884)

• joint contracture
  • adult homozygotes developed joint contractures
  (MGI Ref ID J:53079)

vision/eye phenotype

• ocular hypertension
  • homozygotes showed a significant increase in mean intraocular pressure at 18, 24, and 36 weeks (21%, 44%, and 36%, respectively)
  (MGI Ref ID J:82606)
  • homozygotes displayed an increased accumulation of collagen I in conjunctiva, subconjunctival tissue, and sclera, suggesting an association between IOP regulation and fibrillar collagen turnover
  (MGI Ref ID J:82606)

craniofacial phenotype

• abnormal neurocranium morphology
  • at >4 weeks of age, mutants showed increased bone deposition in calvariae mainly at the inner periosteal surface adjacent to the dura mater
  (MGI Ref ID J:90884)
  • calvarial thickness nearly doubled by ~10 months of age
  (MGI Ref ID J:90884)
  • homozygotes had normal circulating levels of PTH, but showed increased calcein labeling of calvarial surfaces
  (MGI Ref ID J:90884)

• thick neurocranium
  • calvarial thickness nearly doubled by ~10 months of age
  (MGI Ref ID J:90884)

integument phenotype

• focal hair loss
  • heterozygotes developed patchy hair loss
  (MGI Ref ID J:26504)

• thick dermal layer
  • mutant skin displayed a significant increase in collagen extending through to the deep dermis
  (MGI Ref ID J:26504)
  • at ~7 months, heterozygotes developed dermal fibrosis, similar to scleroderma, and skin ulcerations
  (MGI Ref ID J:26504)
  • heterozygous males and females developed similar but milder skin abnormalities relative to age-matched homozygous males
  (MGI Ref ID J:26504)

reproductive system phenotype

• abnormal uterus morphology
  • collagen accumulation in the uteri of heterozygous mutants was less pronounced relative to homozygous mutants
  (MGI Ref ID J:26504)

• decreased litter size
  • heterozygous females had slightly reduced litter sizes and significantly fewer litters than wild-type females
  (MGI Ref ID J:26504)

integument phenotype

• thick dermal layer
  • homozygotes were viable, resistant to collagenase action, and developed normally to young adulthood
  (MGI Ref ID J:26504)
  • at ~7 months, homozygotes developed dermal fibrosis, similar to scleroderma, and skin ulcerations
  (MGI Ref ID J:26504)
  • mutant skin displayed a significant increase in collagen extending through to the deep dermis
  (MGI Ref ID J:26504)
  • homozygous females developed similar but milder skin abnormalities relative to age-matched homozygous males
  (MGI Ref ID J:26504)

• focal hair loss
  • homozygotes developed patchy hair loss
  (MGI Ref ID J:26504)

reproductive system phenotype

• abnormal myometrium morphology
  • occasionally, virgin homozygous females showed small accumulations of collagen in the myometrium of the uterus
  (MGI Ref ID J:26504)

• abnormal uterus morphology
  • homozygous females developed postpartum abnormalities of the uterus, including persistence of nodules containing type I collagen in the uterine wall, caused by a failure of collagen resorption
  (MGI Ref ID J:26504)

• decreased litter size
  • mutant females had slightly reduced litter sizes and significantly fewer litters than wild-type females
  (MGI Ref ID J:26504)