Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names C.RF-Tshrhyt/J    (Changed: 27-NOV-06 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain BALB/cByJ Donor Strain RF/J Generation N10F55pN1 Generation Definitions

Appearance
albino
Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c

Description
Mice homozygous for the hypothyroid spontaneous mutation (Tshr^hyt) are characterized by growth retardation, low thyroid hormone levels, elevated thyroid stimulating hormone (TSH) and hypoplastic thyroid glands. Homozygous mice of both sexes are infertile but fertility as well as growth can be restored by treatment with thyroid hormone. The mice do not respond to exogenous TSH. Homozygous mutant mice also display audiotory defects characterized by morphologic abnormalities of the stereocilia on both inner and outer hair cell systems

Control Information

	Control
	+/? from the colony
	Heterozygote from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Tshr

004858

B6;129S1-Tshrtm1Rmar/J

View Strains carrying other alleles of Tshr     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tshr^hyt/Tshr^hyt

        CBy.RF-Tshr^hyt/J

• nervous system phenotype
• abnormal outer hair cell stereociliary bundle morphology
  • many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants   (MGI Ref ID J:110962)
• • decreased outer hair cell stereocilia number   (MGI Ref ID J:110962)
• decreased cochlear outer hair cell number
  • some missing outer hair cells are noted   (MGI Ref ID J:110962)
• decreased dopaminergic neuron number
  • circling mice have ~40% fewer dopaminergic neurons in the midbrain than wild-type or heterozygotes   (MGI Ref ID J:85902)
  • circling animals appear to have fewer dopaminergic neurons on the left side   (MGI Ref ID J:85902)
• hearing/vestibular/ear phenotype
• abnormal brainstem auditory evoked potential
  • although thresholds improved by approximately 30 dB by P60, residual frequency-dependent deficits of 20-70 dB were observed   (MGI Ref ID J:111112)
  • rate of threshold improvement in mutant mice was approximately ten times slower than in normal mice   (MGI Ref ID J:111112)
• • decreased brainstem auditory evoked potential
    • auditory brainstem response thresholds show significantly elevated mean thresholds (left ear 84.4 dB, right ear 83.9) compared to wild-type (left ear 47.9 dB and 47.5dB)   (MGI Ref ID J:110962)
• abnormal distortion product otoacoustic emission
  • homozygotes display an increased distortion product otoacoustic emission (DPOAE) threshold   (MGI Ref ID J:110962)
  • detection thresholds measured at DPOAE frequencies of 8-18 kHz are significantly higher in mutants than wild-type   (MGI Ref ID J:110962)
  • DPOAE amplitudes are significantly reduced in mutants   (MGI Ref ID J:110962)
• abnormal organ of Corti morphology
  • the tunnel is dysplastic with a very narrow opening whereas the space of Nuel is absent   (MGI Ref ID J:110962)
• • abnormal outer hair cell stereociliary bundle morphology
    • many outer hair cells display a lack of mature appearing stereocilia; a contiguous membrane covers the apex of the ciliary bundles in mutants   (MGI Ref ID J:110962)
  • • decreased outer hair cell stereocilia number   (MGI Ref ID J:110962)
  • decreased cochlear outer hair cell number
    • some missing outer hair cells are noted   (MGI Ref ID J:110962)
• abnormal tectorial membrane morphology
  • in some mutants, the tectorial membrane is shortened and distorted while in others, the membrane is connected to the inner sulcus cells by a fibrillate band   (MGI Ref ID J:110962)
• deafness
  • mutant mice remained profoundly deaf on P24   (MGI Ref ID J:111112)
• immune system phenotype
• decreased B cell number
  • mutants have a lower absolute number of B lineage cells   (MGI Ref ID J:111014)
  • mutant bone marrow B cells have reduced proliferative capacity than wild-type   (MGI Ref ID J:111014)
• increased pro-B cell number
  • pro-B cells from mutant bone marrow show a reduced proliferative capacity   (MGI Ref ID J:111014)
  • thyroxine treated animals show an increase in the number of cycing pro-B cells paralleled by an increase in the total number of pro-B cells   (MGI Ref ID J:111014)
• hematopoietic system phenotype
• decreased B cell number
  • mutants have a lower absolute number of B lineage cells   (MGI Ref ID J:111014)
  • mutant bone marrow B cells have reduced proliferative capacity than wild-type   (MGI Ref ID J:111014)
• increased pro-B cell number
  • pro-B cells from mutant bone marrow show a reduced proliferative capacity   (MGI Ref ID J:111014)
  • thyroxine treated animals show an increase in the number of cycing pro-B cells paralleled by an increase in the total number of pro-B cells   (MGI Ref ID J:111014)
• homeostasis/metabolism phenotype
• decreased circulating progesterone level
  • females show low progesterone levels   (MGI Ref ID J:72929)
• reproductive system phenotype
• abnormal uterine environment
  • females show no implantation   (MGI Ref ID J:72929)
• absent estrous cycle
  • mature mutant females show continuous dioestrus   (MGI Ref ID J:72929)
• decreased ovulation rate
  • a response to gonadotropin treatment is followed by a decrease in ovulation   (MGI Ref ID J:72929)
• impaired luteinization
  • mutants show poor corpus luteum development   (MGI Ref ID J:72929)
• behavior/neurological phenotype
• abnormal frequency of paradoxical sleep   (MGI Ref ID J:72929)
• circling
  • all mice show a strong directional preference (93-100%)   (MGI Ref ID J:85902)
• • unidirectional circling
    • all mice show a strong directional preference (93-100%)   (MGI Ref ID J:85902)
• increased stereotypic behavior
  • mutants can walk in a straight line but when faced with a choice of turning one way or the other always turn in the same direction (same direction as circling behavior)   (MGI Ref ID J:85902)
• growth/size phenotype
• decreased body size
  • 42% of offspring from matings of heterozygous females and homozygous males are small compared to littermates   (MGI Ref ID J:85902)
• • decreased body length
    • body length of homozygotes is less than littermates   (MGI Ref ID J:85902)
  • decreased body weight
    • homozygous mice have reduced body weight compared to wild-type littermates   (MGI Ref ID J:85902)
• cellular phenotype
• increased pro-B cell number
  • pro-B cells from mutant bone marrow show a reduced proliferative capacity   (MGI Ref ID J:111014)
  • thyroxine treated animals show an increase in the number of cycing pro-B cells paralleled by an increase in the total number of pro-B cells   (MGI Ref ID J:111014)

View Research Applications

Research Applications

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

Tshr^hyt related

Endocrine Deficiency Research
Thyroid Defects

Internal/Organ Research
Thyroid Defects

Mouse/Human Gene Homologs
hypothyroidism

Neurobiology Research
Hearing Defects
Receptor Defects

Sensorineural Research
Hearing Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tshrhyt
Allele Name		hypothyroid
Allele Type		Spontaneous
Common Name(s)		hyt; pet; petite;
Strain of Origin		RF/J
Gene Symbol and Name		Tshr, thyroid stimulating hormone receptor
Chromosome		12
Gene Common Name(s)		AI481368; CHNG1; LGR3; TSHRA; expressed sequence AI481368; hTSHR-I; hypothroid; hypothyroid; hyt; pet; petite;
Molecular Note		The mutation in the hypothyroid mouse is a C-to-T transition at nucleotide position 1666. This results in a substitution of a leucine for a proline at position 556 in transmembrane domain IV of the encoded protein. [MGI Ref ID J:16854] [MGI Ref ID J:26725]

Genotyping

Genotyping Information

Genotyping Protocols

Tshr^hyt, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Beamer WJ; Eicher EM; Maltais LJ; Southard JL. 1981. Inherited primary hypothyroidism in mice. Science 212(4490):61-3. [PubMed: 7209519]  [MGI Ref ID J:6479]

Kincaid AE. 2001. Spontaneous circling behavior and dopamine neuron loss in a genetically hypothyroid mouse. Neuroscience 105(4):891-8. [PubMed: 11530227]  [MGI Ref ID J:85902]

O'Malley BW Jr; Li D; Turner DS. 1995. Hearing loss and cochlear abnormalities in the congenital hypothyroid (hyt/hyt) mouse. Hear Res 88(1-2):181-9. [PubMed: 8575993]  [MGI Ref ID J:30383]

Stein SA; Oates EL; Hall CR; Grumbles RM; Fernandez LM; Taylor NA; Puett D; Jin S. 1994. Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol 8(2):129-38. [PubMed: 8170469]  [MGI Ref ID J:16854]

Tshr^hyt related

Bassett JH; Williams AJ; Murphy E; Boyde A; Howell PG; Swinhoe R; Archanco M; Flamant F; Samarut J; Costagliola S; Vassart G; Weiss RE; Refetoff S; Williams GR. 2008. A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism. Mol Endocrinol 22(2):501-12. [PubMed: 17932107]  [MGI Ref ID J:130062]

Beamer WG; Cresswell LA. 1982. Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice. Anat Rec 202(3):387-93. [PubMed: 7072984]  [MGI Ref ID J:6748]

Beamer WG; Eicher EM. 1980. Petite (pet) to hypothyroid (hyt). Mouse News Lett 63:20.  [MGI Ref ID J:13864]

Beamer WJ; Eicher EM; Maltais LJ; Southard JL. 1981. Inherited primary hypothyroidism in mice. Science 212(4490):61-3. [PubMed: 7209519]  [MGI Ref ID J:6479]

Biesiada E; Adams PM; Shanklin DR; Bloom GS; Stein SA. 1996. Biology of the congenitally hypothyroid hyt/hyt mouse. Adv Neuroimmunol 6(4):309-46. [PubMed: 9183515]  [MGI Ref ID J:41267]

Endo T; Kobayashi T. 2008. Thyroid-stimulating hormone receptor in brown adipose tissue is involved in the regulation of thermogenesis. Am J Physiol Endocrinol Metab 295(2):E514-8. [PubMed: 18559984]  [MGI Ref ID J:139995]

Erf GF. 1993. Immune development in young-adult C.RF-hyt mice is affected by congenital and maternal hypothyroidism. Proc Soc Exp Biol Med 204(1):40-8. [PubMed: 8372095]  [MGI Ref ID J:20026]

Foster MP; Jensen ER; Montecino-Rodriguez E; Leathers H; Horseman N; Dorshkind K. 2000. Humoral and cell-mediated immunity in mice with genetic deficiencies of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormone. Clin Immunol 96(2):140-9. [PubMed: 10900161]  [MGI Ref ID J:63735]

Foster MP; Montecino-Rodriguez E; Dorshkind K. 1999. Proliferation of bone marrow pro-B cells is dependent on stimulation by the pituitary/thyroid axis. J Immunol 163(11):5883-90. [PubMed: 10570273]  [MGI Ref ID J:111014]

Gu WX; Du GG; Kopp P; Rentoumis A; Albanese C; Kohn LD; Madison LD; Jameson JL. 1995. The thyrotropin (TSH) receptor transmembrane domain mutation (Pro556-Leu) in the hypothyroid hyt/hyt mouse results in plasma membrane targeting but defective TSH binding. Endocrinology 136(7):3146-53. [PubMed: 7789342]  [MGI Ref ID J:26725]

Jiang JY; Imai Y; Umezu M; Sato E. 2001. Characteristics of infertility in female hypothyroid (hyt) mice. Reproduction 122(5):695-700. [PubMed: 11690529]  [MGI Ref ID J:72929]

Karolyi IJ; Dootz GA; Halsey K; Beyer L; Probst FJ; Johnson KR; Parlow AF; Raphael Y; Dolan DF; Camper SA. 2007. Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice. Mamm Genome 18(8):596-608. [PubMed: 17899304]  [MGI Ref ID J:125708]

Khan JY; Rajakumar RA; Devaskar UP; Weissfeld LA; Devaskar SU. 1999. Effect of primary congenital hypothyroidism upon expression of genes mediating murine brain glucose uptake. Pediatr Res 45(5 Pt 1):718-25. [PubMed: 10231871]  [MGI Ref ID J:55839]

Kincaid AE. 2001. Spontaneous circling behavior and dopamine neuron loss in a genetically hypothyroid mouse. Neuroscience 105(4):891-8. [PubMed: 11530227]  [MGI Ref ID J:85902]

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]

Laffan EW; Lisciotto CA; Gapp DA; Weldon DA. 1989. Development of rotorod performance in normal and congenitally hypothyroid mutant mice. Behav Neural Biol 52(3):411-6. [PubMed: 2590150]  [MGI Ref ID J:32748]

Li D; Henley CM; O'Malley BW Jr. 1999. Distortion product otoacoustic emissions and outer hair cell defects in the hyt/hyt mutant mouse. Hear Res 138(1-2):65-72. [PubMed: 10575115]  [MGI Ref ID J:110962]

Li J; Chow SY. 1994. Subcellular distribution of carbonic anhydrase and Na+,K(+)-ATPase in the brain of the hyt/hyt hypothyroid mice. Neurochem Res 19(1):83-8. [PubMed: 8139768]  [MGI Ref ID J:28518]

Milenkovic M; De Deken X; Jin L; De Felice M; Di Lauro R; Dumont JE; Corvilain B; Miot F. 2007. Duox expression and related H2O2 measurement in mouse thyroid: onset in embryonic development and regulation by TSH in adult. J Endocrinol 192(3):615-26. [PubMed: 17332529]  [MGI Ref ID J:119789]

Montecino-Rodriguez E; Clark RG; Powell-Braxton L; Dorshkind K. 1997. Primary B cell development is impaired in mice with defects of the pituitary/thyroid axis. J Immunol 159(6):2712-9. [PubMed: 9300691]  [MGI Ref ID J:110683]

O'Malley BW Jr; Li D; Turner DS. 1995. Hearing loss and cochlear abnormalities in the congenital hypothyroid (hyt/hyt) mouse. Hear Res 88(1-2):181-9. [PubMed: 8575993]  [MGI Ref ID J:30383]

Postiglione MP; Parlato R; Rodriguez-Mallon A; Rosica A; Mithbaokar P; Maresca M; Marians RC; Davies TF; Zannini MS; De Felice M; Di Lauro R. 2002. Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland. Proc Natl Acad Sci U S A 99(24):15462-7. [PubMed: 12432093]  [MGI Ref ID J:80538]

Sole E; Calvo R; Obregon MJ; Meseguer A. 1996. Effects of thyroid hormone on the androgenic expression of KAP gene in mouse kidney. Mol Cell Endocrinol 119(2):147-59. [PubMed: 8807634]  [MGI Ref ID J:33604]

Sole E; Calvo R; Obregon MJ; Meseguer A. 1994. Thyroid hormone controls the cell-specific expression of the kidney androgen-regulated protein gene in S3 mouse kidney cells. Endocrinology 135(5):2120-9. [PubMed: 7956935]  [MGI Ref ID J:21594]

Song L; McGee JA; Walsh EJ. 2006. Consequences of combined maternal, fetal and persistent postnatal hypothyroidism on the development of auditory function in Tshr(hyt) mutant mice. Brain Res 1101(1):59-72. [PubMed: 16780814]  [MGI Ref ID J:111112]

Southard; Eicher E. 1977. Petite (pet) Mouse News Lett 56:41.  [MGI Ref ID J:32749]

Stein SA; Oates EL; Hall CR; Grumbles RM; Fernandez LM; Taylor NA; Puett D; Jin S. 1994. Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol 8(2):129-38. [PubMed: 8170469]  [MGI Ref ID J:16854]

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]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry

This strain carrying the hypothyroid mutation is maintained by mating heterozygous females with homozygous males. Male mice used for breeding at The Jackson Laboratory are implanted with a 60-day timed-release capsule containing 5 mg of L-thyroxine under the skin. Homozygous females are not used for breeding because implanted L-thyroxine will pass through the milk to nursing pups. Implantation is done under the skin at the back of the neck at 5-7 weeks of age. Some male homozygotes will begin breeding prior to implantation, and if this is the case, we do not use the capsule. Capsules are not replaced at the end of 60 days, but our breeder pairs here at The Jackson Laboratorywill often continue to breed for up to a year. Capsules may be purchased from Innovative Research of America, Sarasota, FL. The Jackson Laboratory does not implant L-thyroxine capsules in male homozygous mice prior to distribution.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Mouse Mutant Resource collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	+/? from the colony
	Heterozygote from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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