Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S1 via W9.5 ES (+Kitl-SlJ) ES cell line Generation N12F?+6pN1   Donating Investigator Douglas Forrest,   National Institutes of Health

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Thrb^tm1Df targeted mutation are viable and fertile displaying normal growth rates. Homozygous mutant mice exhibit goiter and elevated levels of both thyroid hormone and thyroid stimulating hormone. Defects in liver responses to thyroid hormone and subtle behavioral abnormalities are observed. The mice fail to develop normal hearing, as assessed by impaired auditory-evoked brainstem responses, and are susceptible to audiogenic seizures. This strain provides a recessive model for the human syndrome of generalized thyroid hormone resistance (GTHR).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Thyroid Hormone Resistance, Generalized, Autosomal Recessive; GRTH - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Thrb^tm1Df/Thrb^tm1Df

        B6.129S1-Thrb^tm1Df

• hearing/vestibular/ear phenotype
• abnormal cochlear inner hair cell physiology (MGI Ref ID J:118402)
  • at P19, homozygotes display absence of the fast-activating potassium current I_K,f which is associated with IHC maturation and is normally detected by P14 and rises to plateau after P20
• decreased brainstem auditory evoked potential (MGI Ref ID 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 phenotype
• abnormal cochlear inner hair cell physiology (MGI Ref ID J:118402)
  • at P19, homozygotes display absence of the fast-activating potassium current I_K,f which is associated with IHC maturation and is normally detected by P14 and rises to plateau after P20

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Thrb^tm1Df/Thrb⁺

        either: B6.129S1-Thrb^tm1Df or (involves: 129S1/Sv * C57BL/6J)

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:103702)
  • unlike homozygotes, heterozygotes of either genetic background are resistant to audiogenic seizures

Thrb^tm1Df/Thrb^tm1Df

        involves: 129S1/Sv * C57BL/6J

• endocrine/exocrine gland phenotype
• abnormal thyroid follicle morphology (MGI Ref ID J:34421)
  • number and size of follicles both increased
• enlarged thyroid gland (MGI Ref ID J:34421)
  • 1.5-2 fold increase in thyroid size
• thyroid gland hyperplasia (MGI Ref ID J:34421)
• increased activity of thyroid (MGI Ref ID J:34421)
  • hyperactive state with increased epithelial cell turnover
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:34421)
  • 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 mice 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
  • adult homozygotes do not display circling or any other behavioral or neuroanatomical defects
• nervous system phenotype
• abnormal cochlear inner hair cell physiology (MGI Ref ID J:73382)
  • homozygotes exhibit a delay in the induction of the fast-activating potassium current I_K,f which is associated with IHC maturation and is normally induced by P13 and plateaus after P20
  • I_K,f is largely absent at P15-P18, when hearing impairment is first evident in young homozygotes
  • I_K,f eventually appears with a significant delay and reaches half-maximal expression at ~P28
  • at P50, I_K,f approaches magnitudes detected in wild-type IHCs
  • despite retarded expression of I_K,f, development of the endocochlear potential, other hair cell transducer conductances, and OHC electromotility, appear normal
  • 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
• abnormal cochlear outer hair cell physiology (MGI Ref ID J:73382)
• decreased cochlear outer hair cell electromotility (MGI Ref ID J:73382)
  • 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 Thra^tm1Ven and Thrb^tm1Df (87 ± 32 fF/pF)
  • 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
• short cochlear outer hair cells (MGI Ref ID J:118178)
  • at P8, mutant OHCs are smaller than wild-type OHCs, based on linear, voltage-independent capacitances
• hearing/vestibular/ear phenotype
• abnormal cochlear inner hair cell physiology (MGI Ref ID J:73382)
  • homozygotes exhibit a delay in the induction of the fast-activating potassium current I_K,f which is associated with IHC maturation and is normally induced by P13 and plateaus after P20
  • I_K,f is largely absent at P15-P18, when hearing impairment is first evident in young homozygotes
  • I_K,f eventually appears with a significant delay and reaches half-maximal expression at ~P28
  • at P50, I_K,f approaches magnitudes detected in wild-type IHCs
  • despite retarded expression of I_K,f, development of the endocochlear potential, other hair cell transducer conductances, and OHC electromotility, appear normal
  • 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
• abnormal cochlear outer hair cell physiology (MGI Ref ID J:73382)
• decreased cochlear outer hair cell electromotility (MGI Ref ID J:73382)
  • 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 Thra^tm1Ven and Thrb^tm1Df (87 ± 32 fF/pF)
  • 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
• abnormal organ of Corti (MGI Ref ID 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 (MGI Ref ID J:118178)
  • at P8, mutant OHCs are smaller than wild-type OHCs, based on linear, voltage-independent capacitances
• abnormal tectorial membrane morphology (MGI Ref ID 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 (MGI Ref ID J:73382)
  • at P9, the tectorial membrane is slightly enlarged although not to the extent observed in mice that are double homozygous for Thra^tm1Ven and Thrb^tm1Df
  • 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 Thra^tm1Ven and Thrb^tm1Df
• deafness (MGI Ref ID J:63101)
  • homozygotes exhibit a profound hearing loss across a wide range of frequencies
• decreased brainstem auditory evoked potential (MGI Ref ID J:63101)
  • 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)
  • ~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
  • ~10% of adult homozygotes are unresponsive to any stimulus frequency tested at 100 SPL
  • 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)
  • 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
  • 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
• delayed inner ear development (MGI Ref ID J:63101)
  • 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
  • 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 Thra^tm1Ven and Thrb^tm1Df
• homeostasis/metabolism phenotype
• decreased circulating thyroxine level (MGI Ref ID J:34421)
  • T4 levels are reduced at 1.5 years of age
• increased circulating thyroxine level (MGI Ref ID J:34421)
  • elevated serum levels of T4 between 5 and 40 weeks of age
• increased circulating triiodothyronine level (MGI Ref ID J:34421)
  • serum T3 levels elevated
• increased thyroid-stimulating hormone level (MGI Ref ID J:34421)
  • elevated TSH levels are present although no morphological abnormalities are seen in the pituitary

Thrb^tm1Df/Thrb^tm1Df

        either: B6.129S1-Thrb^tm1Df or (involves: 129S1/Sv * C57BL/6J)

• behavior/neurological phenotype
• audiogenic seizures (MGI Ref ID 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 phenotype
• deafness (MGI Ref ID J:103702)
  • at 2 months, homozygotes exhibit residual ABR responses with slightly diminished waveforms, indicating that deafness is severe but not complete
• decreased brainstem auditory evoked potential (MGI Ref ID 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
• homeostasis/metabolism phenotype
• increased circulating thyroxine level (MGI Ref ID J:103702)
  • homozygotes exhibit a ~2-fold increase in total serum T4 levels relative to wild-type mice
• increased circulating triiodothyronine level (MGI Ref ID J:103702)
  • homozygotes exhibit a ~2-fold increase in total serum T3 levels relative to wild-type mice
• increased thyroid-stimulating hormone level (MGI Ref ID J:103702)
  • homozygotes exhibit a ~2-fold increase in total serum TSH levels relative to wild-type mice
• nervous system phenotype
• audiogenic seizures (MGI Ref ID 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

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Thrb^tm1Df related

Endocrine Deficiency Research
Hypothalamus/Pituitary Defects
Thyroid Defects (goiter)
Thyroid Defects (hyperthyroidism)

Internal/Organ Research
Liver Defects
Thyroid Defects (hyperthyroidism)

Mouse/Human Gene Homologs
thyroid hormone resistance, generalized

Neurobiology Research
Epilepsy (audiogenic seizures)
Vestibular and Hearing Defects

Research Tools
Endocrine Deficiency Research
Genetics Research (Mutagenesis and Transgenesis)
Sensorineural Research

Sensorineural Research
Eye Defects
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Thrbtm1Df
Allele Name		targeted mutation 1, Douglas Forrest
Allele Type		Targeted (knock-out)
Common Name(s)		TRbeta-; Thrb-;
Mutation Made By		Douglas Forrest,   National Institutes of Health
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Thrb, thyroid hormone receptor beta
Chromosome		14
Gene Common Name(s)		C-erba-beta; ERBA-BETA; ERBA2; GRTH; MGC126109; MGC126110; NR1A2; PRTH; RATT3REC; T3R[b]; T3Rbeta; T3rec; THR1; THRB1; THRB2; TR beta; TRbeta; Thrb1; Thrb2; c-erbAbeta; thyroid hormone receptor beta 1; thyroid hormone receptor beta 2;
Molecular Note		Insertion of a neomycin cassette into exon 3, disrupts both the beta1 and beta2 isoforms of this gene. RT-PCR analysis identified a short transcript in homozygous mutant mice. Upon sequencing, this transcript revealed a deletion of exon 3 sequences, and fused beta1 exon 2 to exon 4. This results in an aberrant open reading frame, which terminates early into exon 4. No functional protein is predicted from this transcript, as the essential DNA binding and T3 binding domains not present. [MGI Ref ID J:34421]

Genotyping

Genotyping Information

Genotyping Protocols

Thrb^tm1Df, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Forrest D; Hanebuth E; Smeyne RJ; Everds N; Stewart CL; Wehner JM; Curran T. 1996. Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue-specific modulation of receptor function. EMBO J 15(12):3006-15. [PubMed: 8670802]  [MGI Ref ID J:34421]

Additional References

Amma LL; Campos-Barros A; Wang Z; Vennstrom B; Forrest D. 2001. Distinct Tissue-Specific Roles for Thyroid Hormone Receptors beta and alpha1 in Regulation of Type 1 Deiodinase Expression. Mol Endocrinol 15(3):467-75. [PubMed: 11222747]  [MGI Ref ID J:67946]

Forrest D; Erway LC; Ng L; Altschuler R; Curran T. 1996. Thyroid hormone receptor beta is essential for development of auditory function. Nat Genet 13(3):354-7. [PubMed: 8673137]  [MGI Ref ID J:63101]

Forrest D; Vennstrom B. 2000. Functions of thyroid hormone receptors in mice Thyroid 10(1):41-52. [PubMed: 10691312]  [MGI Ref ID J:60449]

Gullberg H; Rudling M; Salto C; Forrest D; Angelin B; Vennstrom B. 2002. Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice. Mol Endocrinol 16(8):1767-77. [PubMed: 12145333]  [MGI Ref ID J:89791]

Johansson C; Gothe S; Forrest D; Vennstrom B; Thoren P. 1999. Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-beta or both alpha1 and beta. Am J Physiol 276(6 Pt 2):H2006-12. [PubMed: 10362681]  [MGI Ref ID J:55864]

Mansen A; Yu F; Forrest D; Larsson L; Vennstrom B. 2001. TRs have common and isoform-specific functions in regulation of the cardiac myosin heavy chain genes. Mol Endocrinol 15(12):2106-14. [PubMed: 11731612]  [MGI Ref ID J:72960]

Salto C; Kindblom JM; Johansson C; Wang Z; Gullberg H; Nordstrom K; Mansen A; Ohlsson C; Thoren P; Forrest D; Vennstrom B. 2001. Ablation of TRalpha2 and a Concomitant Overexpression of alpha1 Yields a Mixed Hypo- and Hyperthyroid Phenotype in Mice. Mol Endocrinol 15(12):2115-28. [PubMed: 11731613]  [MGI Ref ID J:72959]

Thrb^tm1Df related

Abel ED; Ahima RS; Boers ME; Elmquist JK; Wondisford FE. 2001. Critical role for thyroid hormone receptor beta2 in the regulation of paraventricular thyrotropin-releasing hormone neurons. J Clin Invest 107(8):1017-23. [PubMed: 11306605]  [MGI Ref ID J:68885]

Amma LL; Campos-Barros A; Wang Z; Vennstrom B; Forrest D. 2001. Distinct Tissue-Specific Roles for Thyroid Hormone Receptors beta and alpha1 in Regulation of Type 1 Deiodinase Expression. Mol Endocrinol 15(3):467-75. [PubMed: 11222747]  [MGI Ref ID J:67946]

Amma LL; Goodyear R; Faris JS; Jones I; Ng L; Richardson G; Forrest D. 2003. An emilin family extracellular matrix protein identified in the cochlear basilar membrane. Mol Cell Neurosci 23(3):460-72. [PubMed: 12837629]  [MGI Ref ID J:126300]

Barros AC; Erway LC; Krezel W; Curran T; Kastner P; Chambon P; Forrest D. 1998. Absence of thyroid hormone receptor beta-retinoid X receptor interactions in auditory function and in the pituitary-thyroid axis. Neuroreport 9(13):2933-7. [PubMed: 9804293]  [MGI Ref ID J:103717]

Bassett JH; Nordstrom K; Boyde A; Howell PG; Kelly S; Vennstrom B; Williams GR. 2007. Thyroid Status during Skeletal Development Determines Adult Bone Structure and Mineralization. Mol Endocrinol 21(8):1893-1904. [PubMed: 17488972]  [MGI Ref ID J:123118]

Calza L; Forrest D; Vennstrom B; Hokfelt T. 2000. Expression of peptides and other neurochemical markers in hypothalamus and olfactory bulb of mice devoid of all known thyroid hormone receptors. Neuroscience 101(4):1001-12. [PubMed: 11113349]  [MGI Ref ID J:118024]

Dellovade TL; Chan J; Vennstrom B; Forrest D; Pfaff DW. 2000. The two thyroid hormone receptor genes have opposite effects on estrogen-stimulated sex behaviors. Nat Neurosci 3(5):472-5. [PubMed: 10769387]  [MGI Ref ID J:61839]

Dkhissi-Benyahya O; Gronfier C; De Vanssay W; Flamant F; Cooper HM. 2007. Modeling the role of mid-wavelength cones in circadian responses to light. Neuron 53(5):677-87. [PubMed: 17329208]  [MGI Ref ID J:128662]

Forrest D; Erway LC; Ng L; Altschuler R; Curran T. 1996. Thyroid hormone receptor beta is essential for development of auditory function. Nat Genet 13(3):354-7. [PubMed: 8673137]  [MGI Ref ID J:63101]

Furumoto H; Ying H; Chandramouli GV; Zhao L; Walker RL; Meltzer PS; Willingham MC; Cheng SY. 2005. An unliganded thyroid hormone beta receptor activates the cyclin D1/cyclin-dependent kinase/retinoblastoma/E2F pathway and induces pituitary tumorigenesis. Mol Cell Biol 25(1):124-35. [PubMed: 15601836]  [MGI Ref ID J:95391]

Golozoubova V; Gullberg H; Matthias A; Cannon B; Vennstrom B; Nedergaard J. 2004. Depressed thermogenesis but competent brown adipose tissue recruitment in mice devoid of all hormone-binding thyroid hormone receptors. Mol Endocrinol 18(2):384-401. [PubMed: 14630998]  [MGI Ref ID J:87747]

Gothe S; Wang Z; Ng L; Kindblom JM; Barros AC; Ohlsson C; Vennstrom B; Forrest D. 1999. Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation. Genes Dev 13(10):1329-41. [PubMed: 10346821]  [MGI Ref ID J:55414]

Gullberg H; Rudling M; Forrest D; Angelin B; Vennstrom B. 2000. Thyroid hormone receptor beta-deficient mice show complete loss of the normal cholesterol 7alpha-hydroxylase (CYP7A) response to thyroid hormone but display enhanced resistance to dietary cholesterol. Mol Endocrinol 14(11):1739-49. [PubMed: 11075809]  [MGI Ref ID J:125475]

Gullberg H; Rudling M; Salto C; Forrest D; Angelin B; Vennstrom B. 2002. Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice. Mol Endocrinol 16(8):1767-77. [PubMed: 12145333]  [MGI Ref ID J:89791]

Hashimoto K; Cohen RN; Yamada M; Markan KR; Monden T; Satoh T; Mori M; Wondisford FE. 2006. Cross-talk between thyroid hormone receptor and liver X receptor regulatory pathways is revealed in a thyroid hormone resistance mouse model. J Biol Chem 281(1):295-302. [PubMed: 16260782]  [MGI Ref ID J:105670]

Johansson C; Gothe S; Forrest D; Vennstrom B; Thoren P. 1999. Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-beta or both alpha1 and beta. Am J Physiol 276(6 Pt 2):H2006-12. [PubMed: 10362681]  [MGI Ref ID J:55864]

Johansson C; Lannergren J; Lunde PK; Vennstrom B; Thoren P; Westerblad H. 2000. Isometric force and endurance in soleus muscle of thyroid hormone receptor-alpha(1)- or -beta-deficient mice. Am J Physiol Regul Integr Comp Physiol 278(3):R598-603. [PubMed: 10712278]  [MGI Ref ID J:61289]

Johansson C; Lunde PK; Gothe S; Lannergren J; Westerblad H. 2003. Isometric force and endurance in skeletal muscle of mice devoid of all known thyroid hormone receptors. J Physiol 547(Pt 3):789-96. [PubMed: 12562961]  [MGI Ref ID J:105508]

Johnson KR; Zheng QY; Noben-Trauth K. 2006. Strain background effects and genetic modifiers of hearing in mice. Brain Res 1091(1):79-88. [PubMed: 16579977]  [MGI Ref ID J:110459]

Kato Y; Ying H; Willingham MC; Cheng SY. 2004. A tumor suppressor role for thyroid hormone beta receptor in a mouse model of thyroid carcinogenesis. Endocrinology 145(10):4430-8. [PubMed: 15231697]  [MGI Ref ID J:92629]

Kindblom JM; Gevers EF; Skrtic SM; Lindberg MK; Gothe S; Tornell J; Vennstrom B; Ohlsson C. 2005. Increased adipogenesis in bone marrow but decreased bone mineral density in mice devoid of thyroid hormone receptors. Bone 36(4):607-16. [PubMed: 15780976]  [MGI Ref ID J:98068]

Kindblom JM; Kindblom JM; Gothe S; Forrest D; Tornell J; Tornell J; Vennstrom B; Ohlsson C. 2001. GH substitution reverses the growth phenotype but not the defective ossification in thyroid hormone receptor alpha1-/-beta-/- mice. J Endocrinol 171(1):15-22. [PubMed: 11572786]  [MGI Ref ID J:72045]

Knostman KA; Jhiang SM; Capen CC. 2007. Genetic alterations in thyroid cancer: the role of mouse models. Vet Pathol 44(1):1-14. [PubMed: 17197619]  [MGI Ref ID J:129329]

Mansen A; Yu F; Forrest D; Larsson L; Vennstrom B. 2001. TRs have common and isoform-specific functions in regulation of the cardiac myosin heavy chain genes. Mol Endocrinol 15(12):2106-14. [PubMed: 11731612]  [MGI Ref ID J:72960]

Ng L; Pedraza PE; Faris JS; Vennstrom B; Curran T; Morreale de Escobar G; Forrest D. 2001. Audiogenic seizure susceptibility in thyroid hormone receptor beta-deficient mice. Neuroreport 12(11):2359-62. [PubMed: 11496110]  [MGI Ref ID J:103702]

Ng L; Rusch A; Amma LL; Nordstrom K; Erway LC; Vennstrom B; Forrest D. 2001. Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor alpha gene. Hum Mol Genet 10(23):2701-8. [PubMed: 11726557]  [MGI Ref ID J:118402]

Rusch A; Erway LC; Oliver D; Vennstrom B; Forrest D. 1998. Thyroid hormone receptor beta-dependent expression of a potassium conductance in inner hair cells at the onset of hearing. Proc Natl Acad Sci U S A 95(26):15758-62. [PubMed: 9861043]  [MGI Ref ID J:118178]

Rusch A; Erway LC; Vennstrom B; Forrest D. 1998. Thyroid hormone receptor Beta is involved in developmental maturation of inner hair cell ionic conductances Hered Deaf News 15:51.  [MGI Ref ID J:48666]

Rusch A; Ng L; Goodyear R; Oliver D; Lisoukov I; Vennstrom B; Richardson G; Kelley MW; Forrest D. 2001. Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors. J Neurosci 21(24):9792-800. [PubMed: 11739587]  [MGI Ref ID J:73382]

Sandhofer C; Schwartz HL; Mariash CN; Forrest D; Oppenheimer JH. 1998. Beta receptor isoforms are not essential for thyroid hormone-dependent acceleration of PCP-2 and myelin basic protein gene expression in the developing brains of neonatal mice. Mol Cell Endocrinol 137(2):109-15. [PubMed: 9605512]  [MGI Ref ID J:47019]

Suzuki H; Zhang XY; Forrest D; Willingham MC; Cheng SY. 2003. Marked potentiation of the dominant negative action of a mutant thyroid hormone receptor beta in mice by the ablation of one wild-type beta allele. Mol Endocrinol 17(5):895-907. [PubMed: 12576488]  [MGI Ref ID J:83199]

Tinnikov A; Nordstrom K; Thoren P; Kindblom JM; Malin S; Rozell B; Adams M; Rajanayagam O; Pettersson S; Ohlsson C; Chatterjee K; Vennstrom B. 2002. Retardation of post-natal development caused by a negatively acting thyroid hormone receptor alpha1. EMBO J 21(19):5079-87. [PubMed: 12356724]  [MGI Ref ID J:100290]

Wallis K; Sjogren M; van Hogerlinden M; Silberberg G; Fisahn A; Nordstrom K; Larsson L; Westerblad H; Morreale de Escobar G; Shupliakov O; Vennstrom B. 2008. Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneurons caused by an unliganded thyroid hormone receptor alpha1. J Neurosci 28(8):1904-15. [PubMed: 18287507]  [MGI Ref ID J:131713]

Weiss RE; Forrest D; Pohlenz J; Cua K; Curran T; Refetoff S. 1997. Thyrotropin regulation by thyroid hormone in thyroid hormone receptor beta-deficient mice. Endocrinology 138(9):3624-9. [PubMed: 9275045]  [MGI Ref ID J:42911]

Winter H; Braig C; Zimmermann U; Geisler HS; Franzer JT; Weber T; Ley M; Engel J; Knirsch M; Bauer K; Christ S; Walsh EJ; McGee J; Kopschall I; Rohbock K; Knipper M. 2006. Thyroid hormone receptors TRalpha1 and TRbeta differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells. J Cell Sci 119(Pt 14):2975-84. [PubMed: 16803873]  [MGI Ref ID J:111711]

Wistuba J; Mittag J; Luetjens CM; Cooper TG; Yeung CH; Nieschlag E; Bauer K. 2007. Male congenital hypothyroid Pax8-/- mice are infertile despite adequate treatment with thyroid hormone. J Endocrinol 192(1):99-109. [PubMed: 17210747]  [MGI Ref ID J:117324]

Yu F; Gothe S; Wikstrom L; Forrest D; Vennstrom B; Larsson L. 2000. Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles. Am J Physiol Regul Integr Comp Physiol 278(6):R1545-54. [PubMed: 10848522]  [MGI Ref ID J:63071]

Zhang XY; Kaneshige M; Kamiya Y; Kaneshige K; McPhie P; Cheng SY. 2002. Differential expression of thyroid hormone receptor isoforms dictates the dominant negative activity of mutant Beta receptor. Mol Endocrinol 16(9):2077-92. [PubMed: 12198244]  [MGI Ref ID J:78703]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain is maintained by mating homozygous siblings. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.