growth/size/body
• mutants are 17-23% smaller than wild-type at all ages examined
(J:65885)
|
• short body length seen postnatally
|
• mutants exhibit a reduced growth spurt by 25-40% during the age of 3-7 weeks
(J:65885)
• the accelerated growth in utero is followed by a slowing of the growth rate in the postnatal period
(J:84310)
|
• mutants exhibit accelerated growth in utero
|
endocrine/exocrine glands
• 2-fold increase in the number of TSH secreting cells in the pituitary
|
• thyroid gland is about 18-fold larger than in wild-type
|
• extensive hyperplasia of the thyroid gland epithelium
|
• the extremely high TSH level despite increases in thyroid hormone levels, indicate that the pituitary is resistant to the action of thyroid hormone
|
homeostasis/metabolism
• 15-fold increase in the circulating total T4 concentration
(J:65885)
• total T4 levels are elevated 4-, 7-, and 11-fold in neonates, 2 week, and 4 week old homozygotes, respectively; T4 is elevated at time of birth
(J:84310)
|
• 9-fold increase in the circulating total T3 concentration
|
• 412-fold higher serum TSH level than in wild-type
|
skeleton
• neonatal skull has an exaggerated curvature of the cranium
|
short femur
(
J:65885
)
• femurs are 12% shorter
|
short tibia
(
J:65885
)
• tibias are 10% shorter
|
• the length of long bones is increased at E17.5, however at birth, long bone lengths are similar to wild-type and their length is reduced in the early postnatal period, indicating abnormal development of long bones
• increased calcified bone is evident in 2-week old limbs
• mutants exhibit advanced bone formation, leading to growth retardation: by 3 weeks of age, the growth plate is fully organized and the secondary center of ossification that forms the epiphysis of the fibula is present compared to the immature growth plates in wild-type at this time
|
• fontanelles are smaller at E17.5 and in neonates
|
• growth plates are narrower at 2 and 3 weeks of age than in wild-type
• at 3 weeks of age, exhibit early quiescence of the growth plates in the upper and lower limbs
|
• at 2 and 3 weeks of age, the proliferative zone is narrower, however by 4 weeks of age, there is no further narrowing, indicating that the growth plate becomes quiescent between 3 and 4 weeks of age and remains broader instead of continuing to narrow as in wild-type
|
• at 2 and 3 weeks, the hypertrophic zone is narrower, however by 4 weeks of age, there is no further narrowing, indicating that the growth plate becomes quiescent between 3 and 4 weeks of age and remains broader instead of continuing to narrow as in wild type
|
• by 2 weeks of age, trabecular bone mineralization is advanced, with increased mineralization at 4 weeks
|
• neonates exhibit advanced endochondral bone formation at 3 weeks of age
• premature formation of the secondary center of ossification in the fibula
|
• neonates exhibit advanced bone formation in the skull of the cranial bones and mandible
|
• craniosynostosis is evident by E17.5 and more pronounced at birth
|
nervous system
• 2-fold increase in the number of TSH secreting cells in the pituitary
|
• the extremely high TSH level despite increases in thyroid hormone levels, indicate that the pituitary is resistant to the action of thyroid hormone
|
limbs/digits/tail
• the upper and lower limbs at E17.5 are larger, however at 3 weeks of age, they are shorter
|
short femur
(
J:65885
)
• femurs are 12% shorter
|
short tibia
(
J:65885
)
• tibias are 10% shorter
|
craniofacial
• neonatal skull has an exaggerated curvature of the cranium
|
• fontanelles are smaller at E17.5 and in neonates
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
thyroid hormone resistance syndrome | DOID:11633 |
OMIM:188570 OMIM:274300 |
J:65885 |