Phenotypes associated with this allele

• Allele Symbol: Thrb^tm1.1Syc
• Allele Name: targeted mutation 1.1, Sheue-yann Cheng
• Allele ID: MGI:2137592
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Thrb^tm1.1Syc/Thrb^tm1.1Syc	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * C57BL/6J	MGI:3715723
hm2	Thrb^tm1.1Syc/Thrb^tm1.1Syc	involves: 129S6/SvEvTac	MGI:3715622
hm3	Thrb^tm1.1Syc/Thrb^tm1.1Syc	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6	MGI:3715647
hm4	Thrb^tm1.1Syc/Thrb^tm1.1Syc	involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss	MGI:3719582
hm5	Thrb^tm1.1Syc/Thrb^tm1.1Syc	involves: 129S6/SvEvTac * FVB/N * NIH Black Swiss	MGI:3715602
hm6	Thrb^tm1.1Syc/Thrb^tm1.1Syc	involves: 129S6/SvEvTac * NIH Black Swiss	MGI:5528981
ht7	Thrb^tm1.1Syc/Thrb^+	involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss	MGI:3721432
ht8	Thrb^tm1.1Syc/Thrb^+	involves: 129S6/SvEvTac * FVB/N * NIH Black Swiss	MGI:3715607
ht9	Thrb^tm1.1Syc/Thrb^+	involves: 129S6/SvEvTac * NIH Black Swiss	MGI:5528982
ht10	Thrb^tm1Df/Thrb^tm1.1Syc	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * C57BL/6J	MGI:3715718

Genotype
MGI:3715723

hm1

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * C57BL/6J

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

mortality/aging

premature death ( J:92629 )

• 50% die by around 11 months of age and none survive beyond 16 months of age

endocrine/exocrine glands

increased thyroid gland weight ( J:92629 )

• weights of thyroid glands increase as mice age

increased thyroid carcinoma incidence ( J:92629 )

• spontaneously develop follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung but not the lymph nodes

neoplasm

increased thyroid carcinoma incidence ( J:92629 )

• spontaneously develop follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung but not the lymph nodes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland follicular carcinoma		DOID:3962	OMIM:188470	J:92629

Genotype
MGI:3715622

hm2

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S6/SvEvTac

cardiovascular system

increased cardiac muscle cell glucose uptake ( J:95397 )

• heart glucose utilization is higher (+87 to +340%), depending on the region of the heart

• however, heart size is normal

muscle

increased cardiac muscle cell glucose uptake ( J:95397 )

• heart glucose utilization is higher (+87 to +340%), depending on the region of the heart

• however, heart size is normal

cellular

increased cardiac muscle cell glucose uptake ( J:95397 )

• heart glucose utilization is higher (+87 to +340%), depending on the region of the heart

• however, heart size is normal

Genotype
MGI:3715647

hm3

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6

endocrine/exocrine glands

enlarged pituitary gland ( J:95391 )

• pituitaries are enlarged 2.2 and 2.7 fold at the ages of 6-8 and 9-13 months, respectively

increased pituitary adenoma incidence ( J:95391 )

• spontaneously develop pituitary adenomas as mutants age; adenomas stain for TSH

homeostasis/metabolism

abnormal pituitary hormone level ( J:95391 )

increased circulating thyroid-stimulating hormone level ( J:95391 )

• serum TSH concentrations at the age of 1-2 months are 1,033-fold higher and at 6-12 months of age, 429- to 623-fold higher

abnormal thyroid hormone level ( J:95391 )

increased circulating thyroxine level ( J:95391 )

• serum total T4 levels at 1-8 months of age is 12.2- to 12.9-fold higher and at the age of 9-12 months, is 10.4-fold higher

increased circulating triiodothyronine level ( J:95391 )

• serum total T3 levels are increased from 17.2-fold at the ages of 1-2 months to 33.1- and 34.2-fold in older mice

neoplasm

increased pituitary adenoma incidence ( J:95391 )

• spontaneously develop pituitary adenomas as mutants age; adenomas stain for TSH

nervous system

enlarged pituitary gland ( J:95391 )

• pituitaries are enlarged 2.2 and 2.7 fold at the ages of 6-8 and 9-13 months, respectively

increased pituitary adenoma incidence ( J:95391 )

• spontaneously develop pituitary adenomas as mutants age; adenomas stain for TSH

Genotype
MGI:3719582

hm4

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss

skeleton

short tibia ( J:103351 )

• tibias are 11% shorter at 2 weeks of age and only 2% shorter at 4 weeks, indicating an accelerated growth spurt between these ages

premature endochondral bone ossification ( J:103351 )

• E17.5 and P1 skeletons show advanced endochondral ossification and are larger than wild-type

premature intramembranous bone ossification ( J:103351 )

• advanced ossification of the skull

premature cranial suture closure ( J:103351 )

limbs/digits/tail

short tibia ( J:103351 )

• tibias are 11% shorter at 2 weeks of age and only 2% shorter at 4 weeks, indicating an accelerated growth spurt between these ages

hearing/vestibular/ear

abnormal cochlea morphology ( J:124153 )

• defects in cochlear morphogenesis become evident between P0/P1 and 3 weeks of age

abnormal organ of Corti morphology ( J:124153 )

• at 6 weeks, neither the tunnel of Corti nor the space of Nuel appear to have opened though both inner and outer pillar cells are present in the middle cochlear turn

• at this age, inner and outer pillar cells are not easily recognizable and the fluid spaces are reduced in the basal turn

cochlear hair cell degeneration ( J:124153 )

• at 6 weeks, homozygotes show a highly variable loss of cochlear hair cells ranging from a normal complement to almost complete degeneration in both apical and basal turns

organ of Corti degeneration ( J:124153 )

• at 6 weeks, an almost complete degeneration of the organ of Corti is noted in the apical cochlear turn

• cells are present along the basilar membrane but no specific cell types are identified

abnormal tectorial membrane morphology ( J:124153 )

• at 6 weeks, the tectorial membrane is significantly thickened and shortened, possibly due to the membrane folding back upon itself

detached tectorial membrane ( J:124153 )

• at 6 weeks, the tectorial membrane does not appear to contact the organ of Corti in any turns of the cochlea

enlarged tectorial membrane ( J:124153 )

• at 6 weeks, the tectorial membrane is enlarged throughout the cochlear duct; however, a consistent gradient in morphology is observed

• in the basal turn, the tectorial membrane displays the smallest degree of thickening but the highest degree of folding

• in the middle turn, the degree of membrane thickening is increased relative to the basal turn but the level of folding is slightly reduced

• in the apical turn, the highest degree of thickening is observed though the amount of folding is minimal

increased or absent threshold for auditory brainstem response ( J:124153 )

• at 3 and 6 weeks of age, homozygotes display significantly elevated ABR thresholds (72-98 dB SPL) in response to click, 8-, 16- and 32-kHz pure tone stimuli relative to wild-type (22-44 dB SPL) or heterozygous (23-43 dB SPL) littermates

impaired hearing ( J:124153 )

• at 6 weeks of age, homozygotes display a severe to profound hearing loss at all test frequencies

• however, no circling, head tossing or other behaviors suggestive of vestibular dysfunction are observed

nervous system

cochlear hair cell degeneration ( J:124153 )

• at 6 weeks, homozygotes show a highly variable loss of cochlear hair cells ranging from a normal complement to almost complete degeneration in both apical and basal turns

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:124153

Genotype
MGI:3715602

hm5

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S6/SvEvTac * FVB/N * NIH Black Swiss

Histology of thyroid glands of wild-type, Thrb^tm1.1Syc/Thrb⁺ and Thrb^tm1.1Syc/Thrb^tm1.1Syc mice.

growth/size/body

decreased body size ( J:65885 , J:84310 )

• mutants are 17-23% smaller than wild-type at all ages examined (J:65885)

decreased body length ( J:84310 )

• short body length seen postnatally

postnatal growth retardation ( J:65885 , J:84310 )

• 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)

abnormal fetal growth/weight/body size ( J:84310 )

• mutants exhibit accelerated growth in utero

endocrine/exocrine glands

increased thyrotroph cell number ( J:65885 )

• 2-fold increase in the number of TSH secreting cells in the pituitary

enlarged thyroid gland ( J:65885 )

• thyroid gland is about 18-fold larger than in wild-type

thyroid gland hyperplasia ( J:65885 )

• extensive hyperplasia of the thyroid gland epithelium

abnormal pituitary gland physiology ( J:65885 )

• 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

abnormal circulating hormone level ( J:65885 )

increased circulating thyroid-stimulating hormone level ( J:65885 )

• 412-fold higher serum TSH level than in wild-type

increased circulating thyroxine level ( J:65885 , J:84310 )

• 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)

increased circulating triiodothyronine level ( J:65885 )

• 9-fold increase in the circulating total T3 concentration

skeleton

abnormal cranium morphology ( J:84310 )

• 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

abnormal skeleton development ( J:84310 )

• 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

small fontanelles ( J:84310 )

• fontanelles are smaller at E17.5 and in neonates

abnormal epiphyseal plate morphology ( J:84310 )

• 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

abnormal long bone epiphyseal plate proliferative zone ( J:84310 )

• 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

abnormal long bone hypertrophic chondrocyte zone ( J:84310 )

• 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

abnormal bone mineralization ( J:84310 )

• by 2 weeks of age, trabecular bone mineralization is advanced, with increased mineralization at 4 weeks

premature endochondral bone ossification ( J:84310 )

• neonates exhibit advanced endochondral bone formation at 3 weeks of age

• premature formation of the secondary center of ossification in the fibula

premature intramembranous bone ossification ( J:84310 )

• neonates exhibit advanced bone formation in the skull of the cranial bones and mandible

premature cranial suture closure ( J:84310 )

• craniosynostosis is evident by E17.5 and more pronounced at birth

nervous system

increased thyrotroph cell number ( J:65885 )

• 2-fold increase in the number of TSH secreting cells in the pituitary

abnormal pituitary gland physiology ( J:65885 )

• 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

abnormal limb morphology ( J:84310 )

• 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

abnormal cranium morphology ( J:84310 )

• neonatal skull has an exaggerated curvature of the cranium

small fontanelles ( J:84310 )

• 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

Genotype
MGI:5528981

hm6

• Allelic Composition: Thrb^tm1.1Syc/Thrb^tm1.1Syc
• Genetic Background: involves: 129S6/SvEvTac * NIH Black Swiss

behavior/neurological

abnormal habituation ( J:114325 )

♂ • males, but not females, habituate less after multiple sessions of exploratory locomotor activity

impaired learning ( J:114325 )

• females require more sessions to reach criterion of greater than 80% hits on three consecutive sessions of the vigilance task, indicating impaired leaning on a task that requires sustained attention

• females exhibit faster reaction times under baseline conditions during the vigilance task

• male vigilance is unaffected by treatment with the psychostimulant methylphenidate unlike in wild-type mice or mutant females which show impaired vigilance performance in response to methylphenidate

decreased vertical activity ( J:114325 )

♀ • females rear less than wild-type females

hyperactivity ( J:114325 )

• males, but not females, exhibit hyperactivity after multiple sessions of exploratory locomotor activity (after habituation)

• males exhibit a faster rate of acquisition of a nose-poke response on the response acquisition task, however, they also respond more than wild-type mice in the inactive nose-poke hole, indicating a greater baseline response rate inside the operant-conditioning chambers and males show a decrease in inactive response rate after multiple session and perform similarly to controls, suggesting that differences in acquisition are due to increased activity and not to improved learning

• during the first 3 sessions of response acquisition, females show a greater rate of responding in the inactive nose-poke holes than wild-type females but do not differ in the rate of change over multiple sessions, suggesting hyperactivity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
attention deficit hyperactivity disorder		DOID:1094	OMIM:143465 OMIM:608903 OMIM:608904 OMIM:608905 OMIM:608906 OMIM:612311 OMIM:612312	J:114325
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:114325

Genotype
MGI:3721432

ht7

• Allelic Composition: Thrb^tm1.1Syc/Thrb⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:124153 )

N • at 3 weeks or 4 months of age, heterozygotes display normal auditory function, with no significant differences in ABR threholds in response to click, 8-, 16- and 32-kHz pure tone stimuli relative to wild-type mice

Genotype
MGI:3715607

ht8

• Allelic Composition: Thrb^tm1.1Syc/Thrb⁺
• Genetic Background: involves: 129S6/SvEvTac * FVB/N * NIH Black Swiss

Histology of thyroid glands of wild-type, Thrb^tm1.1Syc/Thrb⁺ and Thrb^tm1.1Syc/Thrb^tm1.1Syc mice.

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:65885 )

• increase in the size of individual follicles of the thyroid gland

enlarged thyroid gland ( J:65885 )

• thyroid gland is about 2.4-fold larger than in wild-type

abnormal pituitary gland physiology ( J:65885 )

• the increase in TSH level despite increases in thyroid hormone levels, indicate that the pituitary is resistant to the action of thyroid hormone

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:65885 )

• TSH is 2.1-fold higher than in wild-type

increased circulating thyroxine level ( J:65885 )

• 2.5-fold higher circulating T4 concentration than in wild-type

increased circulating triiodothyronine level ( J:65885 )

• 2-fold increase in the circulating total T3 concentration

skeleton

short femur ( J:65885 )

• femurs are 4% shorter

short tibia ( J:65885 )

• tibias are 5% shorter

limbs/digits/tail

short femur ( J:65885 )

• femurs are 4% shorter

short tibia ( J:65885 )

• tibias are 5% shorter

nervous system

abnormal pituitary gland physiology ( J:65885 )

• the increase in TSH level despite increases in thyroid hormone levels, indicate that the pituitary is resistant to the action of thyroid hormone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:65885

Genotype
MGI:5528982

ht9

• Allelic Composition: Thrb^tm1.1Syc/Thrb⁺
• Genetic Background: involves: 129S6/SvEvTac * NIH Black Swiss

behavior/neurological

abnormal habituation ( J:114325 )

♂ • males habituate less after multiple sessions of exploratory locomotor activity

impaired learning ( J:114325 )

♂ • males are slower to reach criterion, requiring more sessions to reach criterion of greater than 80% hits on three consecutive sessions of the vigilance task, indicating impaired leaning on a task that requires sustained attention

Genotype
MGI:3715718

ht10

• Allelic Composition: Thrb^tm1Df/Thrb^tm1.1Syc
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * C57BL/6J

mortality/aging

premature death ( J:92629 )

• begin to die at about 5 months of age; 50% die by around 11 months of age and none survive beyond 16 months of age

endocrine/exocrine glands

enlarged thyroid gland ( J:92629 )

• 10- and 41-fold increase in the size of thyroid glands at 3-6 months of age and 12-15 months of age, respectively

increased thyroid carcinoma incidence ( J:92629 )

• spontaneously develop follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung but not the lymph nodes

respiratory system

respiratory distress ( J:92629 )

• respiratory distress due to the compression of the trachea by he enlarged thyroid glands

neoplasm

increased thyroid carcinoma incidence ( J:92629 )

• spontaneously develop follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung but not the lymph nodes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland follicular carcinoma		DOID:3962	OMIM:188470	J:92629