All Phenotypes Thra<tm1Syc> MGI Mouse

postnatal growth retardation ( J:103351 )

abnormal long bone diaphysis morphology ( J:217018 )

• bones exhibit abnormal cross-section throughout the diaphysis

abnormal long bone epiphyseal plate morphology ( J:103351 )

• 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

abnormal long bone epiphyseal ossification zone morphology ( J:103351 )

• reduced ossification of the secondary tibial epiphyses

abnormal long bone epiphyseal plate proliferative zone ( J:103351 )

• the PZ region is 5% narrower than in controls

decreased width of hypertrophic chondrocyte zone ( J:103351 )

• the HZ region is 10% narrower than in controls

increased long bone epiphyseal plate size ( J:217018 )

• 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

abnormal long bone metaphysis morphology ( J:217018 )

• bones exhibit splayed metaphyses

decreased length of long bones ( J:217018 )

• bones from 14 and 20 week old mice are 17% and 15% shorter, respectively

short ulna ( J:103351 )

• ulnas are 12-14% shorter

short tibia ( J:103351 )

• tibias are 15-25% shorter than tibias at all postnatal ages examined, however no differences at E17.5 or P1 are seen

increased diameter of long bones ( J:217018 )

• 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

abnormal bone structure ( J:103351 )

decreased osteoclast cell number ( J:217018 )

• 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

abnormal bone mineral content ( J:217018 )

• mice have an increase in bone mineral content despite a reduction in tissue mineralization density

decreased bone mineral content ( J:217018 )

• lower bone mineral content at 14 weeks of age

increased bone mineral content ( J:217018 )

• 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

abnormal compact bone morphology ( J:103351 )

• cortical bone deposition in the tibial diaphysis is reduced by about 50% in 2 week old heterozygotes

increased compact bone volume ( J:217018 )

increased compact bone thickness ( J:217018 )

• 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

abnormal trabecular bone morphology ( J:103351 )

• reduction in deposition of calcified trabecular bone at 2 weeks of age

increased trabecular bone volume ( J:217018 )

• trabecular bone volume is increased 2.1-fold in 20 week old mice

increased bone trabecula number ( J:217018 )

• trabecula number is increased 1.9-fold in 20 week old mice

increased trabecular bone thickness ( J:217018 )

• trabecular bone thickness is increased 1.1-fold in 20 week old mice

abnormal joint morphology ( J:217018 )

• bones exhibit misshapen joint surfaces

large fontanelles ( J:103351 )

• fontanelles are larger in neonates

wide cranial sutures ( J:103351 )

• cranial sutures are wider than in wild-type at E17.5 and in neonates

abnormal bone mineralization ( J:103351 , J:217018 )

	• reduction in trabecular bone mineralization (J:103351)
	• 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)

delayed endochondral bone ossification ( J:103351 , J:217018 )

• 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)

• 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)

delayed intramembranous bone ossification ( J:103351 )

• intramembranous bone deposited in frontal and parietal bones is more porous and stains less intensely, indicating delayed intramembranous ossification of the skull

delayed cranial suture closure ( J:103351 )

abnormal bone remodeling ( J:217018 )

• 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

abnormal osteoclast physiology ( J:217018 )

• reduction in osteoclastic bone resorption

decreased bone resorption ( J:217018 )

• reduction in osteoclastic bone resorption, however bone formation parameters are similar to wild-type mice

abnormal bone strength ( J:217018 )

• mice show normal bone strength, however prolonged T4 treatment results in increased bone stiffness and strength

decreased osteoclast cell number ( J:217018 )

• 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

abnormal osteoclast physiology ( J:217018 )

• reduction in osteoclastic bone resorption

abnormal hormone level ( J:217018 )

• 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

increased triiodothyronine level ( J:217018 )

• basal T3 levels are increased by 1.5-fold

• however, basal T4 levels do not differ from wild-type mice

increased thyroid-stimulating hormone level ( J:217018 )

• 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

decreased osteoclast cell number ( J:217018 )

• 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

abnormal osteoclast physiology ( J:217018 )

• reduction in osteoclastic bone resorption

short ulna ( J:103351 )

• ulnas are 12-14% shorter

short tibia ( J:103351 )

• tibias are 15-25% shorter than tibias at all postnatal ages examined, however no differences at E17.5 or P1 are seen

large fontanelles ( J:103351 )

• fontanelles are larger in neonates

wide cranial sutures ( J:103351 )

• cranial sutures are wider than in wild-type at E17.5 and in neonates

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

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

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

Contributing Projects: 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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