All Phenotypes Thra<tm1Ven> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Thra^tm1Ven/Thra^tm1Ven	involves: 129P2/OlaHsd * BALB/c	MGI:3606706
ht2	Thra^tm1Ven/Thra^tm3Ven	involves: 129P2/OlaHsd * C57BL/6NCrl	MGI:3606069
cx3	Thra^tm1Ven/Thra^tm1Ven Thrb^tm1Df/Thrb^tm1Df	B6.129-Thra^tm1Ven Thrb^tm1Df	MGI:3698827
cx4	Thra^tm1Ven/Thra^tm1Ven Thrb^tm1Df/Thrb⁺	B6.129-Thra^tm1Ven Thrb^tm1Df	MGI:3698828
cx5	Thra^tm1Ven/Thra⁺ Thrb^tm1Df/Thrb^tm1Df	B6.129-Thra^tm1Ven Thrb^tm1Df	MGI:3698829
cx6	Thra^tm1Ven/Thra^tm1Ven Thrb^tm1Df/Thrb^tm1Df	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3715649
cx7	Thra^tm1Ven/Thra^tm1Ven Thrb^tm1Df/Thrb^tm1Df	involves: 129P2/OlaHsd * 129S1/Sv * BALB/c * C57BL/6J	MGI:3698837

Allelic Composition	Thra^tm1Ven/Thra^tm1Ven
Genetic Background	involves: 129P2/OlaHsd * BALB/c

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Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thra^tm1Ven mutation (1 available); any Thra mutation (40 available)

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

endocrine/exocrine glands

decreased activity of thyroid gland ( J:45675 )

• mutant male mice had lower levels of free T4 than control animals

• no significant differences were found between the female mutant homozygous mice and control

• the T3 level were normal in all mice

• the thyroid glands of mutant mice are normal histologically and no goitre has been detected during 18 month observation

cardiovascular system

decreased heart rate ( J:45675 )

• mutant mice have a lower mean heart rate

• daily injection of T3 resulted in an increase in heart rate but failed to reach the same heart rate as the control group

prolonged QT interval ( J:45675 )

• mutant mice have prolonged QRS- and QTend-interval

• the QTend duration is markedly prolonged in mutant mice suggesting slow ventricular repolarization

homeostasis/metabolism

decreased body temperature ( J:45675 )

• 24 h mean body temperature, recorded by the telemetry system, is 0.5 degree C lower in the mutant than the controls

behavior/neurological

behavior/neurological phenotype ( J:103702 )

N	• homozygotes show no significant incidence of audiogenic seizure susceptibility above the 27% incidence noted in background-matched wild-type mice

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:48666 , J:118178 )

(J:48666)

• at 2-3 months of age, homozygotes exhibit normal auditory-evoked brainstem response (ABR) thresholds for click, 8-, 16-, and 32-kHz frequency stimuli (J:118178)

• in accord with normal ABRs, mutant IHCs show normal developmental expression of the fast-activating potassium current I_K,f at the onset of hearing, indicating normal IHC physiology (J:118178)

abnormal cochlear outer hair cell morphology ( J:111711 )

• despite lack of evidence for a role in hearing, Thra appears to be involved in the final differentiation of cochlear OHCs, as shown by studies of KCNQ4 and prestin protein expression under conditions of goitrogen-induced hypothyroidism

nervous system

abnormal cochlear outer hair cell morphology ( J:111711 )

Allelic Composition	Thra^tm1Ven/Thra^tm3Ven
Genetic Background	involves: 129P2/OlaHsd * C57BL/6NCrl

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thra^tm1Ven mutation (1 available); any Thra mutation (40 available)
Thra^tm3Ven mutation (0 available); any Thra mutation (40 available)

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

growth/size/body

decreased body weight ( J:100290 )

• compound heterozygous mutants exhibited 35% less body weight at 35 days of age compared with simple heterozygous Thra^tm1Ven/Thra⁺ controls

• 70-day-old heterozygous mice weighed only 16% less than simple heterozygous Thra^tm1Ven/Thra⁺ controls

abnormal postnatal growth ( J:100290 )

• delayed eye opening

Allelic Composition	Thra^tm1Ven/Thra^tm1Ven Thrb^tm1Df/Thrb^tm1Df
Genetic Background	B6.129-Thra^tm1Ven Thrb^tm1Df

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Thra^tm1Ven mutation (1 available); any Thra mutation (40 available)
Thrb^tm1Df 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 Thrb^tm1Df 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

decreased follicle stimulating hormone level ( J:117324 )

decreased growth hormone level ( J:117324 )

decreased luteinizing hormone level ( J:117324 )

decreased prolactin level ( J:117324 )

increased thyroid-stimulating hormone level ( J:117324 )

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

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

Find Mice

♀	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)

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

Find Mice

♀	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 Thrb^tm1Df homozygotes and double homozygotes

Allelic Composition	Thra^tm1Ven/Thra^tm1Ven Thrb^tm1Df/Thrb^tm1Df
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

♀	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 Thrb^tm1.1Syc homozygotes

♀	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 Thrb^tm1Df 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 I_K,f relative to single Thrb^tm1Df homozygotes

• at P25, the fast component I_K,f is largely absent in double homozygous mutant IHCs, but eventually rises at later postnatal ages

abnormal cochlear outer hair cell physiology ( J:73382 )

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 Thrb^tm1Df 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 I_K,f relative to single Thrb^tm1Df homozygotes

• at P25, the fast component I_K,f is largely absent in double homozygous mutant IHCs, but eventually rises at later postnatal ages

abnormal cochlear outer hair cell physiology ( J:73382 )

decreased cochlear outer hair cell electromotility ( J:73382 )

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:73382 )

• double homozygotes are viable but prone to die under anesthesia

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