Phenotypes associated with this allele

• Allele Symbol: Thra⁺
• Allele Name: wild type
• Allele ID: MGI:2432229
• Summary: 23 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Thra^tm1b(EUCOMM)Wtsi/Thra^+	C57BL/6N-Thra^tm1b(EUCOMM)Wtsi/Ics	MGI:5757806
ht2	Thra^tm1b(EUCOMM)Wtsi/Thra^+	C57BL/6N-Thra^tm1b(EUCOMM)Wtsi/J	MGI:6263682
ht3	Thra^em1Ffla/Thra^+	C57BL/6-Thra^em1Ffla	MGI:6317178
ht4	Thra^em2Ffla/Thra^+	C57BL/6-Thra^em2Ffla	MGI:6317180
ht5	Thra^em3Ffla/Thra^+	C57BL/6-Thra^em3Ffla	MGI:6317182
ht6	Thra^em4Ffla/Thra^+	C57BL/6-Thra^em4Ffla	MGI:6317184
ht7	Thra^em5Ffla/Thra^+	C57BL/6-Thra^em5Ffla	MGI:6317186
ht8	Thra^tm2Ven/Thra^+	involves: 129P2/OlaHsd * BALB/c	MGI:3701137
ht9	Thra^tm4.1Ven/Thra^+	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6NCrl * FVB/N	MGI:4847955
ht10	Thra^tm3Ven/Thra^+	involves: 129P2/OlaHsd * C57BL/6NCrl	MGI:3606065
ht11	Thra^tm1Brnt/Thra^+	involves: 129S4/SvJae * C57BL/6	MGI:2679065
ht12	Thra^tm1Syc/Thra^+	involves: 129S6/SvEvTac	MGI:3715621
ht13	Thra^tm1Syc/Thra^+	involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss	MGI:3719479
ht14	Thra^tm1Syc/Thra^+	involves: 129S6/SvEvTac * NIH Black Swiss	MGI:3715465
cn15	Tg(Nes-cre)1Kln/0 Thra^tm1Ffla/Thra^+	involves: 129 * C57BL/6 * SJL	MGI:6317188
cn16	Tg(Nes-cre)1Kln/0 Thra^em6Ffla/Thra^+	involves: 129 * C57BL/6 * SJL	MGI:6317187
cn17	Tg(CAG-cre/Esr1*)5Amc/? Thra^tm1Ffla/Thra^+	involves: 129/Sv * C57BL/6 * CBA	MGI:3758925
cn18	Thra^tm1Ffla/Thra^+ Tg(Sycp1-cre)4Min/?	involves: 129/Sv * C57BL/6 * DBA/2	MGI:3758926
cx19	Thra^tm1Ven/Thra^+ Thrb^tm1Df/Thrb^tm1Df	B6.129-Thra^tm1Ven Thrb^tm1Df	MGI:3698829
cx20	Thra^tm3Ven/Thra^+ Thrb^tm1Df/Thrb^+	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl	MGI:3606079
cx21	Thra^tm3Ven/Thra^+ Thrb^tm1Df/Thrb^tm1Df	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl	MGI:3606081
cx22	Thra^tm2Ven/Thra^+ Thrb^tm1Df/Thrb^tm1Df	involves: 129P2/OlaHsd * BALB/c * C57BL/6J	MGI:3700829
cx23	Thra^tm1Jas/Thra^+ Thrb^tm1Olc/Thrb^tm1Olc	involves: 129/Sv * 129S1/Sv * 129X1/SvJ	MGI:4358578

Genotype
MGI:5757806

ht1

• Allelic Composition: Thra^{tm1b(EUCOMM)Wtsi}/Thra⁺
• Genetic Background: C57BL/6N-Thra^{tm1b(EUCOMM)Wtsi}/Ics
• Cell Lines: EPD0204_5_F02

Data Sources

IMPC Data for Thra

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

adipose tissue

decreased total body fat amount ( J:211773 )

IMPC - ICS

behavior/neurological

abnormal contextual conditioning behavior ( J:211773 )

IMPC - ICS

decreased exploration in new environment ( J:211773 )

IMPC - ICS

decreased startle reflex ( J:211773 )

♂

IMPC - ICS

limb grasping ( J:211773 )

IMPC - ICS

decreased grip strength ( J:211773 )

IMPC - ICS

hyperactivity ( J:211773 )

IMPC - ICS

increased vertical activity ( J:211773 )

IMPC - ICS

cardiovascular system

abnormal heart left ventricle morphology ( J:211773 )

IMPC - ICS

growth/size/body

decreased body length ( J:211773 )

♀

IMPC - ICS

hematopoietic system

increased hematocrit ( J:211773 )

IMPC - ICS

homeostasis/metabolism

increased circulating creatinine level ( J:211773 )

IMPC - ICS

increased blood urea nitrogen level ( J:211773 )

IMPC - ICS

increased circulating alkaline phosphatase level ( J:211773 )

IMPC - ICS

improved glucose tolerance ( J:211773 )

♂

IMPC - ICS

limbs/digits/tail

short tibia ( J:211773 )

♂

IMPC - ICS

skeleton

short tibia ( J:211773 )

♂

IMPC - ICS

vision/eye

abnormal retina inner nuclear layer morphology ( J:211773 )

IMPC - ICS

decreased total retina thickness ( J:211773 )

IMPC - ICS

Genotype
MGI:6263682

ht2

• Allelic Composition: Thra^{tm1b(EUCOMM)Wtsi}/Thra⁺
• Genetic Background: C57BL/6N-Thra^{tm1b(EUCOMM)Wtsi}/J
• Cell Lines: EPD0204_5_A03

Data Sources

IMPC Data for Thra

behavior/neurological

increased startle reflex ( J:211773 )

♂

IMPC - JAX

hyperactivity ( J:211773 )

IMPC - JAX

skeleton

abnormal bone structure ( J:211773 )

IMPC - JAX

increased bone mineral content ( J:211773 )

IMPC - JAX

increased bone mineral density ( J:211773 )

IMPC - JAX

Genotype
MGI:6317178

ht3

• Allelic Composition: Thra^em1Ffla/Thra⁺
• Genetic Background: C57BL/6-Thra^em1Ffla

skeleton

skeleton phenotype ( J:268664 )

N • tibia lengths and bone thickness are normal

short femur ( J:268664 )

• in female and male mice

decreased trabecular bone thickness ( J:268664 )

• with increased trabecular bone surface

delayed endochondral bone ossification ( J:268664 )

• incomplete ossification in long bones at P15 with persistence of thick cartilage plates at the extremities, particularly in the tail

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:268664 )

N • mice exhibit normal IL1beta serum levels

increased triiodothyronine level ( J:268664 )

• modest increase of free T3

hematopoietic system

decreased hemoglobin content ( J:268664 )

• slight without a change in spleen size

cellular

abnormal enterocyte proliferation ( J:268664 )

• decreased proliferation of cells in the colon and ileum

digestive/alimentary system

abnormal enterocyte proliferation ( J:268664 )

• decreased proliferation of cells in the colon and ileum

limbs/digits/tail

short femur ( J:268664 )

• in female and male mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:268664

Genotype
MGI:6317180

ht4

• Allelic Composition: Thra^em2Ffla/Thra⁺
• Genetic Background: C57BL/6-Thra^em2Ffla

skeleton

skeleton phenotype ( J:268664 )

N • tibia lengths are normal

short femur ( J:268664 )

• in female and male mice

decreased trabecular bone thickness ( J:268664 )

• with increased trabecular bone surface

delayed endochondral bone ossification ( J:268664 )

• incomplete ossification in long bones at P15 with persistence of thick cartilage plates at the extremities, particularly in the tail

homeostasis/metabolism

increased triiodothyronine level ( J:268664 )

• modest increase of free T3

hematopoietic system

decreased hemoglobin content ( J:268664 )

• slight without a change in spleen size

cellular

abnormal enterocyte proliferation ( J:268664 )

• decreased proliferation of cells in the colon and ileum

digestive/alimentary system

abnormal enterocyte proliferation ( J:268664 )

• decreased proliferation of cells in the colon and ileum

limbs/digits/tail

short femur ( J:268664 )

• in female and male mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid hormone resistance syndrome		DOID:11633	OMIM:188570 OMIM:274300	J:268664

Genotype
MGI:6317182

ht5

• Allelic Composition: Thra^em3Ffla/Thra⁺
• Genetic Background: C57BL/6-Thra^em3Ffla

skeleton

skeleton phenotype ( J:268664 )

N • mice exhibit normal long bone lengths and trabecular thickness

delayed endochondral bone ossification ( J:268664 )

• incomplete ossification in long bones at P15 with persistence of thick cartilage plates at the extremities

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:268664 )

N • mice exhibit normal free T3 levels and hemoglobin content

Genotype
MGI:6317184

ht6

• Allelic Composition: Thra^em4Ffla/Thra⁺
• Genetic Background: C57BL/6-Thra^em4Ffla

skeleton

skeleton phenotype ( J:268664 )

N • mice exhibit normal long bone lengths and trabecular thickness

delayed endochondral bone ossification ( J:268664 )

• incomplete ossification in long bones at P15 with persistence of thick cartilage plates at the extremities

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:268664 )

N • mice exhibit normal free T3 levels and hemoglobin content

Genotype
MGI:6317186

ht7

• Allelic Composition: Thra^em5Ffla/Thra⁺
• Genetic Background: C57BL/6-Thra^em5Ffla

skeleton

skeleton phenotype ( J:268664 )

N

decreased trabecular bone thickness ( J:268664 )

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:268664 )

N

Genotype
MGI:3701137

ht8

• Allelic Composition: Thra^tm2Ven/Thra⁺
• Genetic Background: involves: 129P2/OlaHsd * BALB/c

endocrine/exocrine glands

abnormal thyroid gland physiology ( J:72959 )

• similar to homozygotes, heterozygotes exhibit a mixed hyper- and hypothyroid phenotype, dependent on the tissue studied

decreased activity of thyroid gland ( J:72959 )

• heterozygotes show signs of hypothyroidism, including significantly reduced levels of free T3 T4, increased fat content, and skeletal defects associated with a late-onset growth retardation

increased activity of thyroid gland ( J:72959 )

• in addition to hypothyroidism, heterozygotes display features of hyperthyroidism, including reduced body weight, elevated heart rate, and increased body temperature

homeostasis/metabolism

decreased circulating thyroxine level ( J:72959 )

• both male and female heterozygotes show significantly reduced free T4 levels in serum, that are intermediate between those of wild-type and homozygous mutant mice

decreased circulating triiodothyronine level ( J:72959 )

• both male and female heterozygotes show significantly reduced free T3 levels in serum, that are intermediate between those of wild-type and homozygous mutant mice

• total T3 levels are significantly reduced only in female heterozygotes

decreased circulating insulin-like growth factor I level ( J:72959 )

• heterozygotes display significantly reduced serum IGF-I levels, that are intermediate between those of wild-type and homozygous mutant mice

increased body temperature ( J:72959 )

• heterozygotes display an increased body temperature (36.7 0.1 C) relative to wild-type mice (36.5 0.1 C)

abnormal thyroid-stimulating hormone level ( J:72959 )

• at 6-20 weeks, both male and female heterozygotes display inappropriately normal serum levels of TSH, suggesting an alteration in the pituitary-thyroid axis

growth/size/body

decreased body weight ( J:72959 )

• both female and male heterozygotes show a slightly reduced body weight from birth to adulthood relative to wild-type mice

obese ( J:72959 )

• adult heterozygotes are obese

postnatal growth retardation ( J:72959 )

• both female and male heterozygotes show a slightly delayed growth spurt during the first 9 weeks of life relative to wild-type mice

skeleton

decreased bone mineral density ( J:72959 )

• heterozygotes display decreased trabecular bone mineral density (BMD), as shown by a 17% reduction in proximal tibia

abnormal compact bone morphology ( J:72959 )

• heterozygotes exhibit decreased tibial cortical bone mineral content relative to wild-type mice

decreased compact bone area ( J:72959 )

• heterozygotes exhibit decreased tibial cortical bone periosteal and endosteal circumferences, and cortical area relative to wild-type mice

abnormal trabecular bone morphology ( J:72959 )

• heterozygotes display decreased trabecular bone mineral density (BMD), as shown by a 17% reduction in proximal tibia

adipose tissue

increased total body fat amount ( J:72959 )

• similar to homozygotes, heterozygotes show a significant increase in fat content (121%) relative to wild-type mice

cardiovascular system

increased heart rate ( J:72959 )

• heterozygotes display a 10% increase in basal heart rate relative to wild-type littemates, despite their lower serum T3 levels

Genotype
MGI:4847955

ht9

• Allelic Composition: Thra^tm4.1Ven/Thra⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6NCrl * FVB/N

homeostasis/metabolism

increased circulating triiodothyronine level ( J:166513 )

• in male mice

Genotype
MGI:3606065

ht10

• Allelic Composition: Thra^tm3Ven/Thra⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6NCrl

growth/size/body

decreased body weight ( J:100290 )

• heterozygous mutants exhibited lower body weight at 10 days after birth and a difference increased to 33% at 30 days of age compared with wt controls

• 90-day-old heterozygous mice weighed only 7% less than wt controls

abnormal postnatal growth ( J:100290 )

• eye opening, bone ossification and development of IgM-positive B cells are delayed by 5-10 days in the juvenile mice

behavior/neurological

abnormal object recognition memory ( J:100910 )

• using the novel object recognition task to measure visual recognition memory, mutant 12-14-wk-old mice displayed a memory impairment

• administration of T3 in drinking water during adulthood restored normal recognition memory

• administration of TS during juveniles failed to correct the memory impairment

increased anxiety-related response ( J:100910 )

• 12-14-wk-old mutant mice exhibited a reduced exploratory activity in a brightly lit open field

• 12-14-wk-old mutant mice exhibited a pronounced tendency for retropulsion and a strongly increased freezing behavior

• 12-14-wk-old mutant exhibited increased anxiety-like behavior in the elevated plus maze

• administration of T3 in drinking water during adulthood abolished the abnormal exploratory activity and anxiety but not freezing behavior

• administration of T3 during P10-P35 failed to ameliorate abnormal exploratory and anxiety behaviors

abnormal locomotor coordination ( J:100910 )

• 12-14-wk-old mutant male animals had significantly reduced locomotor coordination on rotarod test

• administration of T3 and T4 during P10-P35 fully restored locomotor ability

• administration of T3 in drinking water during adulthood failed to enhance the locomotor ability

• no difference was seen between wild-type and mutant female mice

nervous system

abnormal cerebellum external granule cell layer morphology ( J:100910 )

• the mutant mice had a delay of 4-6 days in the post-natal migration of cerebellar external granular cells to the internal granular layer

• no obvious abnormalities were found among adult mutant cerebellum by histological analyses

abnormal hippocampus morphology ( J:100910 )

• mutant mice displayed a 40-50% reduction in the number of parvalbumin (PV)-positive cell bodies that was resulted from a reduction in the number of the subpopulation of GABAergic interneurons

Genotype
MGI:2679065

ht11

• Allelic Composition: Thra^tm1Brnt/Thra⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

adipose tissue

increased total body fat amount ( J:85803 )

• total body adipose tissue in males is 4.4-fold greater than in wild-type

increased epididymal fat pad weight ( J:85803 )

growth/size/body

increased body weight ( J:85803 )

• males show increased body weight after 2-3 months of age, however females are normal in size

homeostasis/metabolism

impaired adaptive thermogenesis ( J:85803 )

• after cold exposure for 8 hours, core temperature of mutants drops significantly more than in wild-type

increased circulating thyroxine level ( J:85803 )

• T4 concentration is slightly elevated at 3 months of age

increased circulating triiodothyronine level ( J:85803 )

• serum T3 concentration is increased 14% at 3 months of age

increased circulating glucose level ( J:85803 )

• glucose level is 26% higher than in wild-type

• after an 18-hour fast, glucose level is 55% higher than in wild-type mice

increased circulating insulin level ( J:85803 )

• increase in plasma insulin levels under fasting conditons

increased circulating leptin level ( J:85803 )

• serum leptin levels are 5-fold greater than in wild-type at 3 months of age

increased circulating thyroid-stimulating hormone level ( J:85803 )

• 3.4 fold increase relative to control

• TSH levels are higher at 3 months of age than at 10 months of age

decreased core body temperature ( J:85803 )

• core temperature of mutants is 0.5 degrees Celcius lower than in wild-type mice

insulin resistance ( J:85803 )

• due to reduced catecholamine-stimulated lipolysis

abnormal enzyme/coenzyme activity ( J:85803 )

• alpha-glycerol phosphate dehydrogenase activity in the liver is reduced 30% at 3 months of age and 50% in older mice

impaired lipolysis ( J:85803 )

• mutants exhibit reduced sensitivity to catecholamine-stimulated lipolysis

behavior/neurological

decreased food intake ( J:85803 )

• consumption of food is 65% of wild-type

cardiovascular system

decreased heart rate ( J:85803 )

• heart rate at 3 months of age is reduced by 14% compared to wild-type mice

renal/urinary system

oliguria ( J:85803 )

• urine production is 37% of wild-type

reproductive system

reduced fertility ( J:85803 )

digestive/alimentary system

abnormal defecation ( J:85803 )

• feces production is 48% of wild-type

integument

delayed hair appearance ( J:85803 )

• mutants frequently show delayed hair growth, with some mice having no body hair for up to 8 weeks of age

Genotype
MGI:3715621

ht12

• Allelic Composition: Thra^tm1Syc/Thra⁺
• Genetic Background: involves: 129S6/SvEvTac

cardiovascular system

small heart ( J:95397 )

• heart volume is about 31% lower

decreased cardiac muscle cell glucose uptake ( J:95397 )

• heart glucose utilization is lower (-77 to -95%), depending on the region of the heart

decreased mean systemic arterial blood pressure ( J:95397 )

growth/size/body

decreased body weight ( J:95397 )

• body weight is about 41% lower

muscle

decreased cardiac muscle cell glucose uptake ( J:95397 )

• heart glucose utilization is lower (-77 to -95%), depending on the region of the heart

cellular

decreased cardiac muscle cell glucose uptake ( J:95397 )

• heart glucose utilization is lower (-77 to -95%), depending on the region of the heart

Genotype
MGI:3719479

ht13

• Allelic Composition: Thra^tm1Syc/Thra⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * NIH Black Swiss

growth/size/body

postnatal growth retardation ( J:103351 )

skeleton

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

hematopoietic system

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

homeostasis/metabolism

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

immune system

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

limbs/digits/tail

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

craniofacial

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

Genotype
MGI:3715465

ht14

• Allelic Composition: Thra^tm1Syc/Thra⁺
• Genetic Background: involves: 129S6/SvEvTac * NIH Black Swiss

mortality/aging

premature death ( J:73446 )

• 30% of mutants die; of these, 83% and 96% die by 6 weeks and 11 weeks of age, respectively

growth/size/body

decreased body weight ( J:73446 )

• by 4 weeks of age, weight is about 30% and 40% less in females and males, respectively, than in wild-type

decreased body length ( J:73446 )

• by 4 weeks of age, body length is 15% and 17% shorter in females and males, respectively, than in wild-type

homeostasis/metabolism

increased circulating triiodothyronine level ( J:73446 )

• 15% increase in the mean total T3 concentration

increased circulating thyroid-stimulating hormone level ( J:73446 )

• 1.7-fold higher TSH concentration

endocrine/exocrine glands

decreased activity of thyroid gland ( J:73446 )

• mild thyroid failure

• however, follicular morphology is normal and no lymphoid infiltration is seen in the thyroid glands

reproductive system

reduced fertility ( J:73446 )

• reduced fertility as indicated by decreases in the frequencies of pregnancy and the litter size

reduced female fertility ( J:73446 )

♀

decreased litter size ( J:73446 )

• litter size is reduced from 10-12 to 3-5 per litter

reduced male fertility ( J:73446 )

♂

Genotype
MGI:6317188

cn15

• Allelic Composition: Tg(Nes-cre)1Kln/0; Thra^tm1Ffla/Thra⁺
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:268664 )

nervous system

abnormal cerebellum morphology ( J:268664 )

Genotype
MGI:6317187

cn16

• Allelic Composition: Tg(Nes-cre)1Kln/0; Thra^em6Ffla/Thra⁺
• Genetic Background: involves: 129 * C57BL/6 * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:268664 )

nervous system

abnormal cerebellum morphology ( J:268664 )

Genotype
MGI:3758925

cn17

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/?; Thra^tm1Ffla/Thra⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

nervous system

abnormal cerebellum morphology ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

growth/size/body

abnormal postnatal growth ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

cardiovascular system

abnormal heart rate ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

skeleton

delayed bone ossification ( J:125353 )

• authors state that mice treated at E17.5 with tamoxifen exhibit a phenotype similar but less severe to that observed in Thra^tm1Ffla Tg(Sycp1-cre)4Min mice

Genotype
MGI:3758926

cn18

• Allelic Composition: Thra^tm1Ffla/Thra⁺; Tg(Sycp1-cre)4Min/?
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2

mortality/aging

postnatal lethality, incomplete penetrance ( J:125353 )

• 48% of mice do not reach adulthood

reproductive system

female infertility ( J:125353 )

♀ • despite no obvious defects in ovary morphology, females are sterile

nervous system

abnormal cerebellum external granule cell layer morphology ( J:125353 )

• unlike in wild-type mice, at P21 the external granule layer persists and granular precursor cells are still present

abnormal Purkinje cell dendrite morphology ( J:125353 )

• at P15, arborization of Purkinje cell dendrites is reduced by number and size of dendritic spines

behavior/neurological

ataxia ( J:125353 )

• mice display an ataxic bearing and spread their hindlimbs to maintain their posture

growth/size/body

disproportionate dwarf ( J:125353 )

• while surviving mice gain weight they suffer from a permanent and disproportioned dwarfism

postnatal growth retardation ( J:125353 )

homeostasis/metabolism

impaired adaptive thermogenesis ( J:125353 )

• mice exhibit a defect in thermogenesis such that the body temperature in some mice drops within a few hours after cold exposure

cardiovascular system

increased heart rate ( J:125353 )

• 224+/-24 beats per minute compared to 393+/-45 beats per minute in wild-type mice

irregular heartbeat ( J:125353 )

• mice sometime display cardiac arrhythmia

skeleton

delayed endochondral bone ossification ( J:125353 )

• ossification of the long bones is delayed

hematopoietic system

decreased spleen weight ( J:125353 )

• at P15, spleen weight is decreased (26.9+/-12.2 mg compared to 39.5+/-9.1 mg in wild-type mice)

vision/eye

delayed eyelid opening ( J:125353 )

• eyelid opening was delayed to P25 compared to P15 in wild-type mice

immune system

decreased spleen weight ( J:125353 )

• at P15, spleen weight is decreased (26.9+/-12.2 mg compared to 39.5+/-9.1 mg in wild-type mice)

Genotype
MGI:3698829

cx19

• Allelic Composition: Thra^tm1Ven/Thra⁺; Thrb^tm1Df/Thrb^tm1Df
• Genetic Background: B6.129-Thra^tm1Ven Thrb^tm1Df

hearing/vestibular/ear

increased or absent threshold for auditory brainstem response ( J:73382 )

• on a congenic C57BL/6J background, these mutant mice display ABR thresholds that are intermediate between those of single Thrb^tm1Df homozygotes and double homozygotes

Genotype
MGI:3606079

cx20

• Allelic Composition: Thra^tm3Ven/Thra⁺; Thrb^tm1Df/Thrb⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl

growth/size/body

decreased body weight ( J:100290 )

• male Thra^tm3Ven/Thra⁺ Thrb^tm1Df/Thrb⁺ mutants exhibited 40% less body weight at 31 days of age compared with Thra⁺/Thra⁺ Thrb^tm1Df/Thrb⁺ controls

• similar results were obtained with female mice, although the growth retardation of Thra^tm3Ven/Thra⁺ Thrb^tm1Df/Thrb⁺ mutants was less at 22%

abnormal postnatal growth ( J:100290 )

• the delay in eye opening was partially rescued, occurring at day 15.3 in the Thra^tm3Ven/Thra⁺ Thrb^tm1Df/Thrb⁺ mutants compared with day 18.6 in the Thra⁺/Thra⁺ Thrb^tm1Df/Thrb⁺, and day 14 in the wt mice

Genotype
MGI:3606081

cx21

• Allelic Composition: Thra^tm3Ven/Thra⁺; Thrb^tm1Df/Thrb^tm1Df
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl

growth/size/body

decreased body weight ( J:100290 )

• male Thra^tm3Ven/Thra⁺ Thrb^tm1Df/Thrb^tm1Df mutants exhibited only 14% less body weight at 31 days of age compared with controls

Genotype
MGI:3700829

cx22

• Allelic Composition: Thra^tm2Ven/Thra⁺; Thrb^tm1Df/Thrb^tm1Df
• Genetic Background: involves: 129P2/OlaHsd * BALB/c * C57BL/6J

growth/size/body

postnatal growth retardation ( J:118402 )

• mutant mice exhibit a less severely retarded weight gain over the first 4 postnatal weeks relative to Thra^tm2Ven homozygotes

• no significant difference in postnatal weight gain is noted by 5 weeks

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:118402 )

N • at 7-17 weeks of age, mutant mice display normal ABR thresholds in response to click or pure-tone (8, 16, 32 kHz) stimuli, indicating suppression of the auditory defect observed in single Thrb^tm1Df homozygotes

N • Background Sensitivity: on a mixed genetic background of equal parts 129/Sv, 129OlaHsd, BALB/c, and C57BL/6J strains, ABR responses are similar but more variable than those observed on a congenic C57BL/6J background

N • consistent with rescued ABR thresholds, the developmental expression of the I_K,f potassium current in cochlear IHCs is also largely corrected at P30 relative to single Thrb^tm1Df homozygotes

Genotype
MGI:4358578

cx23

• Allelic Composition: Thra^tm1Jas/Thra⁺; Thrb^tm1Olc/Thrb^tm1Olc
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ

growth/size/body

postnatal growth retardation ( J:52829 )