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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Thrbtm1Df
targeted mutation 1, Douglas Forrest
MGI:1860434
Summary 17 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
 		Thrbtm1Df/Thrbtm1Df B6J.129S1-Thrbtm1Df MGI:3700658
hm2
 		Thrbtm1Df/Thrbtm1Df either: B6.129S1-Thrbtm1Df or (involves: 129S1/Sv * C57BL/6J) MGI:3699104
hm3
 		Thrbtm1Df/Thrbtm1Df involves: 129S1/Sv * C57BL/6J MGI:2657251
hm4
 		Thrbtm1Df/Thrbtm1Df involves: 129S1/Sv * C57BL/6J * FVB/NJ MGI:3836783
ht5
 		Thrbtm1Df/Thrb+ either: B6.129S1-Thrbtm1Df or (involves: 129S1/Sv * C57BL/6J) MGI:3699105
ht6
 		Thrbtm1Df/Thrbtm1.1Syc involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * C57BL/6J MGI:3715718
cn7
 		Thrbtm1Df/Thrbtm1Mkni
Tg(Pres-cre)1Jnz/0 		involves: 129S1/Sv * C57BL/6J * FVB/NJ MGI:3836781
cx8
 		Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrbtm1Df 		B6.129-Thratm1Ven Thrbtm1Df MGI:3698827
cx9
 		Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrb+ 		B6.129-Thratm1Ven Thrbtm1Df MGI:3698828
cx10
 		Thratm1Ven/Thra+
Thrbtm1Df/Thrbtm1Df 		B6.129-Thratm1Ven Thrbtm1Df MGI:3698829
cx11
 		Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrbtm1Df 		involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3715649
cx12
 		Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrbtm1Df 		involves: 129P2/OlaHsd * 129S1/Sv * BALB/c * C57BL/6J MGI:3698837
cx13
 		Thratm3Ven/Thra+
Thrbtm1Df/Thrbtm1Df 		involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl MGI:3606081
cx14
 		Thratm3Ven/Thra+
Thrbtm1Df/Thrb+ 		involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl MGI:3606079
cx15
 		Thratm3Ven/Thratm3Ven
Thrbtm1Df/Thrbtm1Df 		involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl MGI:3606074
cx16
 		Thratm2Ven/Thra+
Thrbtm1Df/Thrbtm1Df 		involves: 129P2/OlaHsd * BALB/c * C57BL/6J MGI:3700829
cx17
 		Thratm2Ven/Thratm2Ven
Thrbtm1Df/Thrbtm1Df 		involves: 129P2/OlaHsd * BALB/c * C57BL/6J MGI:3700828


Genotype
MGI:3700658
hm1
Allelic
Composition		 Thrbtm1Df/Thrbtm1Df
Genetic
Background		 B6J.129S1-Thrbtm1Df
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
homeostasis/metabolism
abnormal response/metabolism to endogenous compounds ( J:222168 )
• both males and females show little or no expansion of the 20-alpha-hydroxysteroid dehydrogenase -positive zone of the adrenal cortex in response to T3 (triiodothyronine) unlike controls which show expansion of this zone when treated with T3 from P14 to P28, indicating resistance to T3 action
• mice are largely resistant to T3-induced hypertrophy of cells in the inner cortical zone from P21 to P35

hearing/vestibular/ear
abnormal cochlear inner hair cell physiology ( J:118402 )
• at P19, homozygotes display absence of the fast-activating potassium current IK,f which is associated with IHC maturation and is normally detected by P14 and rises to plateau after P20
increased or absent threshold for auditory brainstem response ( J:118402 )
• adult homozygotes exhibit significantly increased ABR thresholds for all test stimuli (click, 8-, 16-, and 32-kHz), with waveforms detected only in response to 85 dB SPL vs 40-45 dB SPL in wild-type mice

nervous system
abnormal cochlear inner hair cell physiology ( J:118402 )
• at P19, homozygotes display absence of the fast-activating potassium current IK,f which is associated with IHC maturation and is normally detected by P14 and rises to plateau after P20




Genotype
MGI:3699104
hm2
Allelic
Composition		 Thrbtm1Df/Thrbtm1Df
Genetic
Background		 either: B6.129S1-Thrbtm1Df or (involves: 129S1/Sv * C57BL/6J)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
behavior/neurological
audiogenic seizures ( J:103702 )
• on a mixed genetic background, ~100% of homozygotes display early-onset and persistent auditory seizure susceptibility (AGS) after P16 (but not prior to P11) up to >6 months of age, whereas ~27% of background-matched wild-type show AGS up to 4 weeks but not at 10 months of age
• on a congenic C57BL/6J background, 100% of homozygotes exhibit AGS relative to 0% in congenic wild-type mice

hearing/vestibular/ear
increased or absent threshold for auditory brainstem response ( J:103702 )
• at 2 months, homozygotes exhibit significantly increased ABR thresholds for all test stimuli (click, 8-, 16-, and 32-kHz) relative to wild-type littermates
deafness ( J:103702 )
• at 2 months, homozygotes exhibit residual ABR responses with slightly diminished waveforms, indicating that deafness is severe but not complete

homeostasis/metabolism
increased circulating thyroxine level ( J:103702 )
• homozygotes exhibit a ~2-fold increase in total serum T4 levels relative to wild-type mice
increased circulating triiodothyronine level ( J:103702 )
• homozygotes exhibit a ~2-fold increase in total serum T3 levels relative to wild-type mice
increased thyroid-stimulating hormone level ( J:103702 )
• homozygotes exhibit a ~2-fold increase in total serum TSH levels relative to wild-type mice

nervous system
audiogenic seizures ( J:103702 )
• on a mixed genetic background, ~100% of homozygotes display early-onset and persistent auditory seizure susceptibility (AGS) after P16 (but not prior to P11) up to >6 months of age, whereas ~27% of background-matched wild-type show AGS up to 4 weeks but not at 10 months of age
• on a congenic C57BL/6J background, 100% of homozygotes exhibit AGS relative to 0% in congenic wild-type mice




Genotype
MGI:2657251
hm3
Allelic
Composition		 Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129S1/Sv * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
abnormal thyroid follicle morphology ( J:34421 )
• number and size of follicles both increased
enlarged thyroid gland ( J:34421 )
• 1.5-2 fold increase in thyroid size
increased activity of thyroid gland ( J:34421 )
• hyperactive state with increased epithelial cell turnover

behavior/neurological
behavior/neurological phenotype ( J:34421 , J:63101 )
N
• homozygotes behave normally in learning tests such as the Morris water task and in contextual fear conditioning as well as in open field and Y maze tests (J:34421)
• adult homozygotes do not display circling or any other behavioral or neuroanatomical defects (J:63101)

nervous system
short cochlear outer hair cells ( J:118178 )
• at P8, mutant OHCs are smaller than wild-type OHCs, based on linear, voltage-independent capacitances
abnormal cochlear inner hair cell physiology ( J:48666 , J:73382 , J:118178 )
• in neonatal mutant IHCs, expression of the fast voltage-activated conductance starts ~7 days later and requires >1 month to reach adult wild-type levels (J:48666)
• homozygotes exhibit a delay in the induction of the fast-activating potassium current IK,f which is associated with IHC maturation and is normally induced by P13 and plateaus after P20 (J:73382)
• IK,f is largely absent at P15-P18, when hearing impairment is first evident in young homozygotes (J:118178)
• IK,f eventually appears with a significant delay and reaches half-maximal expression at ~P28 (J:118178)
• at P50, IK,f approaches magnitudes detected in wild-type IHCs (J:118178)
• despite retarded expression of IK,f, development of the endocochlear potential, other hair cell transducer conductances, and OHC electromotility, appear normal (J:118178)
decreased cochlear outer hair cell electromotility ( J:73382 , J:118178 )
• at P8, homozygotes exhibit a slight impairment of electromechanical transduction in OHCs, as shown by slightly reduced nonlinear capacitance (150 46 fF/pF) relative to wild-type mice (290 47 fF/pF) or mice that are double homozygous for for Thratm1Ven and Thrbtm1Df (87 32 fF/pF) (J:73382)
• at P9, homozygotes exhibit a nonlinear capacitance of 271 27 fF/pF, suggesting that differences in voltage-dependent capacitance of mutant OHCs at P8 are not functionally significant (J:118178)

hearing/vestibular/ear
delayed inner ear development ( J:63101 , J:73382 )
• at 15 weeks, adult homozygotes display normal inner ear innervation with no major hypothyroid-like defects in the sensorineural epithelium, tectorial membrane, stria vascularis, or spiral ganglion (J:63101)
• despite an absence of gross cochlear malformations, adult homozygotes exhibit a delay in early postnatal development of the organ of Corti, that is milder than that observed in mice that are double homozygous for Thratm1Ven and Thrbtm1Df (J:73382)
abnormal organ of Corti morphology ( J:73382 )
• at P9, inner sulcus differentiation is delayed, and the tunnel of Corti remains unopened
• at P20, the inner sulcus has opened, but the undelying epithelium is slightly thicker than normal
short cochlear outer hair cells ( J:118178 )
• at P8, mutant OHCs are smaller than wild-type OHCs, based on linear, voltage-independent capacitances
abnormal tectorial membrane striated-sheet matrix morphology ( J:73382 )
• ultrastructurally, adult homozygotes display a mild disorganization of the striated sheet matrix only in the upper regions of the tectorial membrane
enlarged tectorial membrane ( J:73382 )
• at P9, the tectorial membrane is slightly enlarged although not to the extent observed in mice that are double homozygous for Thratm1Ven and Thrbtm1Df
• at P20, the tectorial membrane remains slightly enlarged, although it extends to the hair cells and is not grossly misshapen as in mice that are double homozygous for Thratm1Ven and Thrbtm1Df
abnormal cochlear inner hair cell physiology ( J:48666 , J:73382 , J:118178 )
• in neonatal mutant IHCs, expression of the fast voltage-activated conductance starts ~7 days later and requires >1 month to reach adult wild-type levels (J:48666)
• homozygotes exhibit a delay in the induction of the fast-activating potassium current IK,f which is associated with IHC maturation and is normally induced by P13 and plateaus after P20 (J:73382)
• IK,f is largely absent at P15-P18, when hearing impairment is first evident in young homozygotes (J:118178)
• IK,f eventually appears with a significant delay and reaches half-maximal expression at ~P28 (J:118178)
• at P50, IK,f approaches magnitudes detected in wild-type IHCs (J:118178)
• despite retarded expression of IK,f, development of the endocochlear potential, other hair cell transducer conductances, and OHC electromotility, appear normal (J:118178)
decreased cochlear outer hair cell electromotility ( J:73382 , J:118178 )
• at P8, homozygotes exhibit a slight impairment of electromechanical transduction in OHCs, as shown by slightly reduced nonlinear capacitance (150 46 fF/pF) relative to wild-type mice (290 47 fF/pF) or mice that are double homozygous for for Thratm1Ven and Thrbtm1Df (87 32 fF/pF) (J:73382)
• at P9, homozygotes exhibit a nonlinear capacitance of 271 27 fF/pF, suggesting that differences in voltage-dependent capacitance of mutant OHCs at P8 are not functionally significant (J:118178)
increased or absent threshold for auditory brainstem response ( J:63101 , J:118178 )
• at 9-15 weeks, adult homozygotes show significantly elevated ABR thresholds for a click stimulus (1-16 kHz) and for all test pure tones (8, 16, 32 kHz) (J:63101)
• ~95% of adult homozygotes exhibit ABR thresholds in the 70-100 dB SPL range, while 5% display thresholds in the upper limit of the normal range (J:63101)
• ~10% of adult homozygotes are unresponsive to any stimulus frequency tested at 100 SPL (J:63101)
• young homozygous mutant progeny (P18-P28) display significantly elevated ABR thresholds, independent of the maternal genotype (i.e. homozygous (hyperthyroid) vs heterozygous (euthyroid) mutant mothers) (J:63101)
• although ABR responses are diminished in amplitude, ABR waveforms display a normal pattern of peaks, suggesting that the defect resides in the primary response of the cochlea (J:63101)
• at 2-3 months, homozygotes exhibit significantly elevated ABR thresholds for click, 8-, 16-, and 32-kHz frequency stimuli relative to wild-type or heterozygous littermates (J:118178)
deafness ( J:63101 )
• homozygotes exhibit a profound hearing loss across a wide range of frequencies

homeostasis/metabolism
decreased circulating thyroxine level ( J:34421 )
• T4 levels are reduced at 1.5 years of age
increased circulating thyroxine level ( J:34421 )
• elevated serum levels of T4 between 5 and 40 weeks of age
increased circulating triiodothyronine level ( J:34421 )
• serum T3 levels elevated
increased thyroid-stimulating hormone level ( J:34421 )
• elevated TSH levels are present although no morphological abnormalities are seen in the pituitary

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
thyroid hormone resistance syndrome DOID:11633 OMIM:188570
OMIM:274300
 J:34421 , J:63101




Genotype
MGI:3836783
hm4
Allelic
Composition		 Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129S1/Sv * C57BL/6J * FVB/NJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hearing/vestibular/ear
enlarged tectorial membrane ( J:145941 )
• thickened and enlarged, most prominently in the apical turns
decreased cochlear microphonics ( J:145941 )
• severely reduced
increased or absent threshold for auditory brainstem response ( J:145941 )
• ABR thresholds for click auditory stimuli are increased in mice at 3 - 4 months of age
abnormal cochlear nerve compound action potential ( J:145941 )
• elevated compound action potential thresholds at all frequencies tested in mice at 3 - 4 months of age
• however, the shape of the compound action potential waveform is similar to controls
increased or absent distortion product otoacoustic emission threshold ( J:145941 )
• DPOAE thresholds are altered with no 2f1-f2 amplitude baseline at an f2 frequency of 16 kHz and significantly elevated thresholds at frequencies greater than 8 kHz

nervous system
decreased cochlear microphonics ( J:145941 )
• severely reduced
abnormal cochlear nerve compound action potential ( J:145941 )
• elevated compound action potential thresholds at all frequencies tested in mice at 3 - 4 months of age
• however, the shape of the compound action potential waveform is similar to controls




Genotype
MGI:3699105
ht5
Allelic
Composition		 Thrbtm1Df/Thrb+
Genetic
Background		 either: B6.129S1-Thrbtm1Df or (involves: 129S1/Sv * C57BL/6J)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
behavior/neurological
behavior/neurological phenotype ( J:103702 )
N
• unlike homozygotes, heterozygotes of either genetic background are resistant to audiogenic seizures




Genotype
MGI:3715718
ht6
Allelic
Composition		 Thrbtm1Df/Thrbtm1.1Syc
Genetic
Background		 involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thrbtm1.1Syc mutation (0 available); any Thrb mutation (41 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
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)
follicular thyroid carcinoma DOID:3962 OMIM:188470
 J:92629




Genotype
MGI:3836781
cn7
Allelic
Composition		 Thrbtm1Df/Thrbtm1Mkni
Tg(Pres-cre)1Jnz/0
Genetic
Background		 involves: 129S1/Sv * C57BL/6J * FVB/NJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Pres-cre)1Jnz mutation (0 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
Thrbtm1Mkni mutation (0 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hearing/vestibular/ear
abnormal cochlear inner hair cell physiology ( J:145941 )
• voltage activated K+ currents are absent from inner hair cells
increased or absent threshold for auditory brainstem response ( J:145941 )
• significant increase in ABR thresholds at frequencies less than 8 kHz

nervous system
abnormal cochlear inner hair cell physiology ( J:145941 )
• voltage activated K+ currents are absent from inner hair cells




Genotype
MGI:3698827
cx8
Allelic
Composition		 Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 B6.129-Thratm1Ven Thrbtm1Df
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm1Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hearing/vestibular/ear
abnormal auditory brainstem response ( J:73382 )
• on a congenic C57BL/6J background, adult double homozygotes display significantly exacerbated defects in auditory function relative to single Thrbtm1Df homozygotes, with no detectable ABR waveform for click stimuli at 100 dB SPL, and only weak, atypical waveforms for high-frequency stimuli (16 and 32 kHz) where initial peaks are either absent or delayed
• 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

reproductive system
abnormal sperm motility ( J:117324 )
• postpubertal males show a slight but significant decrease in the swimming velocities of their spermatozoa
• however, testicular histology appears to be complete and fails to show arrested or disorganized tubules; both, the efferent ducts and epididymis appear normal
decreased testis weight ( J:117324 )
• postpubertal males show a significantly decreased testis weight relative to controls
• in contrast, weights of accessory sex glands (seminal vesicles and coagulating glands) are similar to those of wild-type males
female infertility ( J:73382 )
• female double homozygotes are infertile but thrive relatively well

homeostasis/metabolism
abnormal pituitary hormone level ( J:117324 )
• postpubertal males display increased beta-TSH mRNA expression as well as reduced prolactin, growth hormone, luteinizing hormone (beta-LH), follicle-stimulating hormone (beta-FSH), and proopiomelanocortin transcript levels in anterior pituitary

endocrine/exocrine glands
decreased testis weight ( J:117324 )
• postpubertal males show a significantly decreased testis weight relative to controls
• in contrast, weights of accessory sex glands (seminal vesicles and coagulating glands) are similar to those of wild-type males

growth/size/body
decreased body weight ( J:117324 )
• postpubertal male display a significantly reduced body weight relative to controls

cellular
abnormal sperm motility ( J:117324 )
• postpubertal males show a slight but significant decrease in the swimming velocities of their spermatozoa
• however, testicular histology appears to be complete and fails to show arrested or disorganized tubules; both, the efferent ducts and epididymis appear normal




Genotype
MGI:3698828
cx9
Allelic
Composition		 Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrb+
Genetic
Background		 B6.129-Thratm1Ven Thrbtm1Df
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm1Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hearing/vestibular/ear
hearing/vestibular/ear phenotype ( J:73382 )
N
• on a congenic C57BL/6J background, these mutant mice display normal ABR responses to click and pure tone stimuli (8, 16, and 32 kHz)




Genotype
MGI:3698829
cx10
Allelic
Composition		 Thratm1Ven/Thra+
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 B6.129-Thratm1Ven Thrbtm1Df
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm1Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
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 Thrbtm1Df homozygotes and double homozygotes




Genotype
MGI:3715649
cx11
Allelic
Composition		 Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm1Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
small pituitary gland ( J:95391 )
• pituitary size is reduced by 20-30%

homeostasis/metabolism
increased circulating thyroxine level ( J:95391 )
• total T4 is increased 14- to 18-fold from the ages of 1-2 and 9-12 months
increased circulating triiodothyronine level ( J:95391 )
• total T3 is increased from 15.9-fold at 1-2 months of age to 26.4-fold at 9-12 months of age
increased circulating thyroid-stimulating hormone level ( J:95391 )
• serum TSH concentration is increased 728.8- to 56.1-fold at 1-2 months of age and 9-12 months of age, respectively

nervous system
small pituitary gland ( J:95391 )
• pituitary size is reduced by 20-30%

neoplasm
neoplasm ( J:95391 )
N
• do not develop focal adenomas as are seen in Thrbtm1.1Syc homozygotes




Genotype
MGI:3698837
cx12
Allelic
Composition		 Thratm1Ven/Thratm1Ven
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129P2/OlaHsd * 129S1/Sv * BALB/c * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm1Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
increased susceptibility to xenobiotic induced morbidity/mortality ( J:73382 )
• double homozygotes are viable but prone to die under anesthesia

hearing/vestibular/ear
delayed inner ear development ( J:73382 )
• double homozygotes exhibit a significant delay in early postnatal development of the organ of Corti
abnormal organ of Corti morphology ( J:73382 )
• at P8, no inner sulcus is formed and the tunnel of Corti between the inner and outer pillar cells has not opened
• at 7-8 weeks, the tunnel of Corti and inner sulcus have opened, but the tunnel of Corti appears somewhat misshapen
abnormal pillar cell morphology ( J:73382 )
• at P8, pillar cells abnormally protrude above the epithelium between IHCs and OHCs
abnormal tectorial membrane morphology ( J:73382 )
• at P8, the tectorial membrane is deformed and remains attached to the underlying epithelium
• the greater epithelial ridge below the tectorial membrane is significantly thicker than normal
abnormal tectorial membrane striated-sheet matrix morphology ( J:73382 )
• ultrastructurally, 6-month-old double homozygotes display a significant disorganization of the striated sheet matrix throughout the tectorial membrane
enlarged tectorial membrane ( J:73382 )
• at P8, the tectorial membrane is enlarged
• at 7-8 weeks, the tectorial membrane remains enlarged in apical and mid-turns of the cochlea but is often retracted in basal turns
decreased endocochlear potential ( J:73382 )
• adult double homozygotes exhibit a reduced endocochlear potential (52.1 13.6 mV) relative to wild-type mice (92.5 13.5 mV) or single Thrbtm1Df homozygotes (85.2 13.5 mV)
abnormal cochlear inner hair cell physiology ( J:73382 )
• double homozygotes exhibit a similar delay in the induction of the fast-activating potassium current IK,f relative to single Thrbtm1Df homozygotes
• at P25, the fast component IK,f is largely absent in double homozygous mutant IHCs, but eventually rises at later postnatal ages
decreased cochlear outer hair cell electromotility ( J:73382 )
• at P8, double homozygotes exhibit a significant impairment of electromechanical transduction in OHCs, as shown by markedly reduced nonlinear capacitance (87 32 fF/pF) relative to wild-type mice (290 47 fF/pF) or single Thrbtm1Df homozygotes (150 46 fF/pF)

growth/size/body
decreased body size ( J:73382 )
• adult double homozygotes are 30% smaller than wild-type mice

reproductive system
female infertility ( J:73382 )
• female double homozygotes are infertile but thrive relatively well

nervous system
abnormal cochlear inner hair cell physiology ( J:73382 )
• double homozygotes exhibit a similar delay in the induction of the fast-activating potassium current IK,f relative to single Thrbtm1Df homozygotes
• at P25, the fast component IK,f is largely absent in double homozygous mutant IHCs, but eventually rises at later postnatal ages
decreased cochlear outer hair cell electromotility ( J:73382 )
• at P8, double homozygotes exhibit a significant impairment of electromechanical transduction in OHCs, as shown by markedly reduced nonlinear capacitance (87 32 fF/pF) relative to wild-type mice (290 47 fF/pF) or single Thrbtm1Df homozygotes (150 46 fF/pF)

homeostasis/metabolism
increased susceptibility to xenobiotic induced morbidity/mortality ( J:73382 )
• double homozygotes are viable but prone to die under anesthesia




Genotype
MGI:3606081
cx13
Allelic
Composition		 Thratm3Ven/Thra+
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm3Ven mutation (0 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
growth/size/body
decreased body weight ( J:100290 )
• male Thratm3Ven/Thra+ Thrbtm1Df/Thrbtm1Df mutants exhibited only 14% less body weight at 31 days of age compared with controls




Genotype
MGI:3606079
cx14
Allelic
Composition		 Thratm3Ven/Thra+
Thrbtm1Df/Thrb+
Genetic
Background		 involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm3Ven mutation (0 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
growth/size/body
decreased body weight ( J:100290 )
• male Thratm3Ven/Thra+ Thrbtm1Df/Thrb+ mutants exhibited 40% less body weight at 31 days of age compared with Thra+/Thra+ Thrbtm1Df/Thrb+ controls
• similar results were obtained with female mice, although the growth retardation of Thratm3Ven/Thra+ Thrbtm1Df/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 Thratm3Ven/Thra+ Thrbtm1Df/Thrb+ mutants compared with day 18.6 in the Thra+/Thra+ Thrbtm1Df/Thrb+, and day 14 in the wt mice




Genotype
MGI:3606074
cx15
Allelic
Composition		 Thratm3Ven/Thratm3Ven
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6NCrl
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm3Ven mutation (0 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
preweaning lethality, complete penetrance ( J:100290 )
• double homozygous mutant class was not found in intercross between double heterozygote Thratm3Ven/Thra+ Thrbtm1Df/Thrb+ indicating lethality
• actual time of death has not been determined




Genotype
MGI:3700829
cx16
Allelic
Composition		 Thratm2Ven/Thra+
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129P2/OlaHsd * BALB/c * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm2Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
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 Thratm2Ven 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 Thrbtm1Df homozygotes
• 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
• consistent with rescued ABR thresholds, the developmental expression of the IK,f potassium current in cochlear IHCs is also largely corrected at P30 relative to single Thrbtm1Df homozygotes




Genotype
MGI:3700828
cx17
Allelic
Composition		 Thratm2Ven/Thratm2Ven
Thrbtm1Df/Thrbtm1Df
Genetic
Background		 involves: 129P2/OlaHsd * BALB/c * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thratm2Ven mutation (1 available); any Thra mutation (40 available)
Thrbtm1Df mutation (1 available); any Thrb mutation (41 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
growth/size/body
postnatal growth retardation ( J:118402 )
• double homozygotes exhibit a retarded weight gain over the first 5 postnatal weeks, but only to the same extent as in single Thratm2Ven homozygotes
• no significant difference in postnatal weight gain is noted after 5 weeks

endocrine/exocrine glands
abnormal thyroid follicle morphology ( J:118402 )
• similar to Thratm2Ven mice, double homozygotes show thyroid follicles with a somewhat thin, flattened epithelium, but lack the enlargement observed in single Thrbtm1Df homozygotes

homeostasis/metabolism
abnormal thyroid hormone level ( J:118402 )
• similar to Thratm2Ven mice, double homozygotes display normal TSH and slightly low T4 and T3 levels, indicating dominant suppression of the hormonal disorder observed in single Thrbtm1Df homozygotes
decreased circulating thyroxine level ( J:118402 )
• similar to Thratm2Ven mice, double homozygotes display serum free T4 levels that are slightly but significantly below wild-type levels
decreased circulating triiodothyronine level ( J:118402 )
• similar to Thratm2Ven mice, double homozygotes display free T3 levels that are slightly but significantly below wild-type levels; total T3 is also slightly lowered

hearing/vestibular/ear
hearing/vestibular/ear phenotype ( J:118402 )
N
• at 7-17 weeks of age, double homozygotes 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 Thrbtm1Df homozygotes
• 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
• consistent with rescued ABR thresholds, the developmental expression of the IK,f potassium current in cochlear IHCs is also largely corrected at P30 relative to single Thrbtm1Df homozygotes




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Send questions and comments to User Support. 		last database update
11/12/2024
MGI 6.24 		The Jackson Laboratory