Analysis Tools
growth/size/body
skeleton
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• fontanelles are larger in neonates
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• bones exhibit abnormal cross-section throughout the diaphysis
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• at 7 weeks of age, the growth plate is wider than in controls, similar to the width seen at 4 weeks of age in wild-type
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• reduced ossification of the secondary tibial epiphyses
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• the PZ region is 5% narrower than in controls
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• the HZ region is 10% narrower than in controls
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• growth plates in 14 and 20 week old mice are 39% and 70% wider, respectively, than in wild-type mice, indicating persistent delay of endochondral ossification
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• bones exhibit splayed metaphyses
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• bones from 14 and 20 week old mice are 17% and 15% shorter, respectively
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short ulna
(
J:103351
)
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• ulnas are 12-14% shorter
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short tibia
(
J:103351
)
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• tibias are 15-25% shorter than tibias at all postnatal ages examined, however no differences at E17.5 or P1 are seen
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• periosteal diameter is 13% and 20% larger at 14 and 20 weeks of age, respectively
• T4 treatment does not change endosteal diameter compared to a 16% increase in wild-type mice
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• osteoclast surfaces are reduced and fewer osteoclasts are present, with mice having a smaller proportion of their increased bone surface covered by osteoclasts
• T4 treatment accentuates the osteoclast phenotype
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• mice have an increase in bone mineral content despite a reduction in tissue mineralization density
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• lower bone mineral content at 14 weeks of age
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• higher bone mineral content at 20 weeks of age
• supraphysiological T4 treatment further increases bone mineral content in mutants unlike in wild-type mice which show reduced bone mineral content after treatment, indicating that mice are resistant to T4-induced bone loss
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• cortical bone deposition in the tibial diaphysis is reduced by about 50% in 2 week old heterozygotes
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• cortical bone thickness is 48% and 43% wider at 14 and 20 weeks of age, respectively
• T4 treatment has no effect on these bone abnormalities but results in a gradual increase in cortical bone thickness and diameter
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• reduction in deposition of calcified trabecular bone at 2 weeks of age
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• trabecular bone volume is increased 2.1-fold in 20 week old mice
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• trabecula number is increased 1.9-fold in 20 week old mice
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• trabecular bone thickness is increased 1.1-fold in 20 week old mice
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• bones exhibit misshapen joint surfaces
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• cranial sutures are wider than in wild-type at E17.5 and in neonates
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• reduction in trabecular bone mineralization
(J:103351)
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• cortical and trabecular bone mineralization density is reduced in 20 week old mice, with greater reduction in cortical bone; T4 treatment does not affect mineralization
(J:217018)
• mice have an increase in bone mineral content but bone is less mineralized
(J:217018)
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• small delay in endochondrial ossification in the ulna and radius of the forelimb and in the tibia and fibula of the hindlimb at E17.5 and in neonates
(J:103351)
• endochondrial ossification is delayed by 3 to 4 weeks in adult mutants, resulting in smaller tibias in all directions, delayed development of the second ossification center, of the growth plate and subsequent growth plate narrowing
(J:103351)
• hindlimb paws at 3 and 7 weeks of age show impaired endochondral bone formation with delayed formation of secondary ossification centers in metatarsal bones at 2 weeks and the presence of open metatarsal growth plates at 7 weeks
(J:103351)
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• growth plates in 14 and 20 week old mice are 39% and 70% wider, respectively, than in wild-type mice, indicating persistent delay of endochondral ossification
(J:217018)
• T4 treatment does not have an effect on the delayed endochondral ossification
(J:217018)
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• intramembranous bone deposited in frontal and parietal bones is more porous and stains less intensely, indicating delayed intramembranous ossification of the skull
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• increase in retention of mineralized cartilage within trabeculae in 14 and 20 week old mice, indicating impaired bone modeling
• T4 treatment does not have an effect on the impaired bone remodeling
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• reduction in osteoclastic bone resorption
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• reduction in osteoclastic bone resorption, however bone formation parameters are similar to wild-type mice
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• mice show normal bone strength, however prolonged T4 treatment results in increased bone stiffness and strength
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hematopoietic system
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• osteoclast surfaces are reduced and fewer osteoclasts are present, with mice having a smaller proportion of their increased bone surface covered by osteoclasts
• T4 treatment accentuates the osteoclast phenotype
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• reduction in osteoclastic bone resorption
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homeostasis/metabolism
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• reduction in T4:T3 ratio
• supraphysiological T4 treatment attenuates the increases in circulating T4 and T3 concentrations that are seen in wild-type mice, indicating resistance to T4 administration
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• basal TSH levels are increased by 6-fold
• supraphysiological T4 treament from weaning at 4 weeks of age until analysis at 20 weeks of age completely suppresses TSH is both wild-type and heterozygotes
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• basal T3 levels are increased by 1.5-fold
• however, basal T4 levels do not differ from wild-type mice
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immune system
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• osteoclast surfaces are reduced and fewer osteoclasts are present, with mice having a smaller proportion of their increased bone surface covered by osteoclasts
• T4 treatment accentuates the osteoclast phenotype
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• reduction in osteoclastic bone resorption
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limbs/digits/tail
short ulna
(
J:103351
)
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• ulnas are 12-14% shorter
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short tibia
(
J:103351
)
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• tibias are 15-25% shorter than tibias at all postnatal ages examined, however no differences at E17.5 or P1 are seen
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craniofacial
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• cranial sutures are wider than in wild-type at E17.5 and in neonates
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• fontanelles are larger in neonates
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