Go to JAX® Mice Query Form

Strain Name:

B6;129S1-Tshrtm1Rmar/J

Stock Number:

004858

Availability:

Repository-Cryopreserved


Price and Supply Information

General Terms and Conditions

Genes & Alleles   Tshr;   Tshrtm1Rmar;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Terry Davies,   Mount Sinai School of Medicine

Strain Description
Mice that are homozygous for the targeted mutation exhibit delayed eye opening, are runted by day 21, and will die within 1 week if weaned at day 21. Homozygotes will survive by extending weaning to 28 days but will not reproduce. Homozygotes are viable and fertile when weaned at day 21 and subsequently placed on a hormone replacement therapy diet consisting of a 100ppm desiccated thyroid powder supplement. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of thyroid membranes. Enhanced Green Fluorescent Protein (EGFP) gene product is detected by RT-PCR and Western blot analysis of thyroid tissue. Hypothyroidism is exhibited by mutant mice that have a longer weaning period and a non-supplemented diet, as indicated by low T4 and T3 serum levels, and high thyrotropin (TSH) serum levels. Treatment with exogenous TSH does not result in a thyroid hormone release response. Mutant mice produce uniodinated thyroglobulin and do not accumulate radioactive iodide in their thyroid glands, although in vitro cultured thyroid slices have restored iodide uptake ability when cultured in the presence of forskolin (an adenylate cyclase agonist). Sodium-iodide symporter (NIS) protein is undetectable in thyroid tissue by Western blot analysis. Histological examination of mutant thyroid tissue reveals reduced size (approximately 50% of wildtype) and number of follicles. EGFP is detected by fluorescence microscopy in thyroid glands of both homozygotes and heterozygotes. This mutant mouse strain may be useful in studies of hypothyroidism.

Strain Development
A targeting vector containing an Enhanced Green Fluorescent Protein-neomycin resistance cassette (EGFP-neo, Clonetech) and herpes simplex virus thymidine kinase gene was used to disrupt exon 1 of the targeted gene. The construct was electroporated into 129S1/Sv-p+ Tyr+ KitlSl-J/+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animals were crossed to C57BL/6J mice. Heterozygotes were intercrossed to generate homozygotes.

Mammalian Phenotype Terms assigned by genotype

Tshrtm1Rmar/Tshrtm1Rmar

        involves: 129S1/Sv * C57BL/6J
  • lethality-postnatal
  • lethality at weaning (MGI Ref ID J:80513)
    • die within 1 week of weaning unless fed a diet supplemented with thyroid powder
    • mutants can also survive when the preweaning period is extended to P28
  • growth/size phenotype
  • postnatal growth retardation (MGI Ref ID J:80513)
    • developmental and growth delays
  • homeostasis/metabolism phenotype
  • abnormal thyroid hormone level (MGI Ref ID J:80513)
    • decreased circulating levels of thyroid hormone (MGI Ref ID J:80513)
      • hypothyroid with no detectable thyroid hormone, however when mutants are fed normal diet with a high dose thyroid supplement, they become hyperthyroid and TSH levels are suppressed, indicating that the normal feedback mechanism regulating thyroid hormone secretion remains intact
      • decreased circulating thyroxine level (MGI Ref ID J:80513)
        • mutants rescued by prolonged weaning and maintained on a normal diet exhibit low serum T4 levels
      • decreased circulating triiodothyronine level (MGI Ref ID J:80513)
        • mutants rescued by prolonged weaning and maintained on a normal diet exhibit low serum T3 levels
  • increased circulating thyroid-stimulating hormone level (MGI Ref ID J:80513)
    • untreated mutants and mutants rescued by prolonged weaning and maintained on a normal diet exhibit elevated TSH levels
  • endocrine/exocrine gland phenotype
  • abnormal thyroid follicle morphology (MGI Ref ID J:80513)
    • thyroids have fewer follicles and more non-follicle associated cells within the gland than in wild type
  • abnormal thyroid physiology (MGI Ref ID J:80513)
    • mutants fail to release thyroid hormone into the circulation in response to exogenous TSH
    • decreased activity of thyroid (MGI Ref ID J:80513)
      • hypothyroid with no detectable thyroid hormone and elevated TSH, however when placed on thyroid hormone replacement therapy from weaning, mutants become euthyroid
      • mutants rescued by prolonged weaning and maintained on a normal diet are severely hypothyroid as indicated by low serum T4 and T3 levels and elevated TSH levels
    • iodide oxidation defect (MGI Ref ID J:80513)
      • thyroid glands produce uniodinated thyroglobulin, but the ability to concentrate and organify iodide can be restored to thyroids when cultured in the presence of the adenylate cyclase agonist forskolin
  • small thyroid gland (MGI Ref ID J:80513)
    • thyroids are about 50% of the size of normal thyroids
  • reproductive system phenotype
  • reduced fertility (MGI Ref ID J:80513)
    • mutants that survive due to prolonged preweaning period do not reproduce, however mutants supplemented with thyroid powder are fertile

Gene & Allele Details

Allele Symbol Tshrtm1Rmar
Allele Name targeted mutation 1, Russell Marians
Common Name(s) TSHR-KO;
Mutation Made By Russell Marians,  
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line NameW9.5/W95
ES Cell Line Strain129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Site of ExpressionThyroid tissue
Gene Symbol and Name Tshr, thyroid stimulating hormone receptor
Chromosome 12
Gene Common Name(s) AI481368; LGR3; MGC75129; TSHRA; expressed sequence AI481368; hTSHR-I; hypothroid; hypothyroid; hyt; pet; petite;
Molecular Note The endogenous locus was disrupted by an EGFP-neo cassette inserted by homologous recombination. The absence of normal transcript and protein in homozygous mutant mice was demonstrated by RT-PCR and Western blot analyses. GFP expression was confirmed at both the transcript and protein levels. [MGI Ref ID J:80513]

Control Information

  Control
   101043 B6129SF1/J (approximate)
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for JAX® GEMM® Strains

Genotyping Protocols

Tshrtm1Rmar

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as heterozygotes or homozygotes. If weaned at 21 d, homozygous mice die within 1 week unless placed on a hormone replacement therapy diet consisting of 100 ppm dessicated thyroid powder (see Marians PNAS 2002 99:15776-81). Further, homozygotes will survive by extending weaning to 28 days but will not reproduce.

Related Strains

Fluorescent Protein Strains
006053   129-Gt(ROSA)26Sortm1Luo/J
006067   129-Gt(ROSA)26Sortm2Luo/J
006041   129-Gt(ROSA)26Sortm3Luo/J
005483   129-Tg(CAG-EYFP)7AC5Nagy/J
003960   129S6-Tg(Prnp-GFP/cre)1Blw/J
006102   B10.Cg-H2k Tg(Il2/NFAT-luc)83Rinc/J
006100   B10.Cg-H2k Tg(NFkB/Fos-luc)26Rinc/J
005999   B6(SJL)-Tg(SBE/Tk-luc)7Twc/J
004218   B6.129(ICR)-Tg(CAG-ECFP)CK6Nagy/J
006071   B6.129-Gt(ROSA)26Sortm1Luo/J
006080   B6.129-Gt(ROSA)26Sortm2Luo/J
006075   B6.129-Gt(ROSA)26Sortm3Luo/J
006412   B6.129-Il12btm1Lky/J
008451   B6.129P(Cg)-Ptprca Cx3cr1tm1Litt/LittJ
005582   B6.129P-Cx3cr1tm1Litt/J
007572   B6.129P2(Cg)-Rorctm2Litt/J
005693   B6.129P2-Cxcr6tm1Litt/J
007669   B6.129S4-Pdgfratm11(EGFP)Sor/J
006852   B6.129S6-Per2tm1Jt/J
006148   B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J
003479   B6.C3-Tg(Fos-luc)1Rnd/J
006772   B6.Cg-Foxp3tm2Tch/J
005670   B6.Cg-Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
005491   B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
005622   B6.Cg-Shhtm1(EGFP/cre)Cjt/J
007484   B6.Cg-Tyrc-2J Tg(Tyr)3412ARpw Tg(Sry-EGFP)92Ei/EiJ
006055   B6.Cg-Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
004178   B6.Cg-Tg(CAG-Bgeo/GFP)21Lbe/J
006051   B6.Cg-Tg(CAG-DsRed*MST)1Nagy/J
005884   B6.Cg-Tg(CAG-mRFP1)1F1Hadj/J
006069   B6.Cg-Tg(HIST1H2BB/EGFP)1Pa/J
005029   B6.Cg-Tg(Hlxb9-GFP)1Tmj/J
006098   B6.Cg-Tg(Il2/NFAT-luc)83Rinc/J
006864   B6.Cg-Tg(Ins1-EGFP)1Hara/J
005244   B6.Cg-Tg(Krt1-15-EGFP)2Cot/J
007902   B6.Cg-Tg(RP23-268L19-EGFP)2Mik/J
007894   B6.Cg-Tg(Rgs4-EGFP)4Lvt/J
006361   B6.Cg-Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/J
004659   B6.Cg-Tg(TIE2GFP)287Sato/1J
006101   B6.Cg-Tg(TRE/Prl-luc)31FlvRinc/J
007901   B6.Cg-Tg(Thy1-Brainbow1.0)HLich/J
007911   B6.Cg-Tg(Thy1-Brainbow1.1)MLich/J
007921   B6.Cg-Tg(Thy1-Brainbow2.1)RLich/J
003710   B6.Cg-Tg(Thy1-CFP)23Jrs/J
007940   B6.Cg-Tg(Thy1-CFP/COX8A)C1Lich/J
007612   B6.Cg-Tg(Thy1-COP4/EYFP)18Gfng/J
007615   B6.Cg-Tg(Thy1-COP4/EYFP)9Gfng/J
005630   B6.Cg-Tg(Thy1-EYFP)15Jrs/J
003709   B6.Cg-Tg(Thy1-YFP)16Jrs/J
005627   B6.Cg-Tg(Thy1-YFP/Syp)10Jrs/J
003782   B6.Cg-Tg(Thy1-YFPH)2Jrs/J
007606   B6.Cg-Tg(Thy1-cre/ESR1,-EYFP)AGfng/J
006000   B6.FVB-Tg(ITGAM-DTR/EGFP)34Lan/J
004509   B6.FVB-Tg(Itgax-DTR/EGFP)57Lan/J
006417   B6.FVB-Tg(Npy-hrGFP)1Lowl/J
005738   B6.FVB-Tg(tetO-EGFP,-Tgfbr2)8Mcle/J
004077   B6;129-Gt(ROSA)26Sortm2Sho/J
008295   B6;129-Syt9tm1Sud/J
006676   B6;129P2-Olfr151tm26Mom/MomJ
006667   B6;129P2-Omptm3Mom/MomJ
007843   B6;129S4-Efnb2tm2Sor/J
008214   B6;129S4-Pou5f1tm2Jae/J
006614   B6;CB-Tg(Thy1-CFP/COX8A)C1Lich/J
006617   B6;CB-Tg(Thy1-CFP/COX8A)S2Lich/J
004966   B6;CBA-Tg(Acrv1-EGFP)2727Redd/J
004654   B6;CBA-Tg(Pou5f1-EGFP)2Mnn/J
007910   B6;CBA-Tg(Thy1-Brainbow1.0)LLich/J
005621   B6;D2-Tg(S100B-EGFP)1Wjt/J
005620   B6;D2-Tg(S100B-EYFP)1Wjt/J
004690   B6;FVB-Tg(Pcp2-EGFP)2Yuza/J
006147   B6;FVB-Tg(Sfpi1,-EGFP)7Dgt/J
006043   B6;SJL-Tg(Oxt/EGFP)AI03Wsy/J
008004   B6;SJL-Tg(Thy1-ECFP/VAMP2)1Sud/J
007610   B6;SJL-Tg(Thy1-cre/ESR1,-EYFP)VGfng/J
007880   B6SJL-Tg(Thy1-Stx1a/EYFP)1Sud/J
007856   B6SJL-Tg(Thy1-Syt1/ECFP)1Sud/J
004190   C.129-Il4tm1Lky/J
005700   C.129P2-Cxcr6tm1Litt/J
006769   C.Cg-Foxp3tm2Tch/J
004512   C.FVB-Tg(Itgax-DTR/EGFP)57Lan/J
008242   C57BL/6-Gt(ROSA)26Sortm1(Ikbkb)Mass/J
006567   C57BL/6-Tg(CAG-EGFP)131Osb/LeySopJ
003291   C57BL/6-Tg(CAG-EGFP)1Osb/J
005070   C57BL/6-Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck/J
004353   C57BL/6-Tg(UBC-GFP)30Scha/J
005706   C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
006618   C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J
006362   C57BL/6J-Tg(CMV-Cox8a/EYFP)17J/J
003927   C57BL/6J-Tg(Sry-EGFP)92Ei/EiJ
007677   CB6-Tg(Gad1-EGFP)G42Zjh/J
007076   CByJ.B6-Tg(UBC-GFP)30Scha/J
003718   FVB-Tg(GadGFP)45704Swn/J
005515   FVB-Tg(ITGAM-DTR/EGFP)34Lan/J
006421   FVB-Tg(Pomc1-hrGFP)1Lowl/J
005125   FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J
006206   FVB.129S6-Gt(ROSA)26Sortm1(HIF1A/luc)Kael/J
003516   FVB.Cg-Tg(CAG-EGFP)B5Nagy/J
007483   FVB.Cg-Tg(Tyr)3412ARpw Tg(Sry-EGFP)92Ei/EiJ
003257   FVB/N-Tg(GFAPGFP)14Mes/J
006698   NOD.Cg-Il4tm1Lky/JbsJ
008173   NOD.Cg-Tg(Ins1-EGFP)1Hara/QtngJ
005076   NOD.Cg-Tg(tetO-EGFP/FADD)1Doi/DoiJ
005082   NOD/ShiLt-Tg(ACTB-Ica1/EGFP)18Mdos/MdosJ
005328   NOD/ShiLt-Tg(Cd4-DsRed)4Lt/J
005334   NOD/ShiLt-Tg(Cd4-EGFP)1Lt/J
005282   NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara/HaraJ
006331   STOCK Gt(ROSA)26Sortm1(DTA)Jpmb/J
005130   STOCK Gt(ROSA)26Sortm1(Smo/EYFP)Amc/J
005572   STOCK Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
007576   STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J
004808   STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
004779   STOCK Mapttm1(EGFP)Klt/J
006741   STOCK Olfr160tm1Mom Tg(Olfr151,taulacZ)BMom/MomJ
006678   STOCK Olfr160tm6Mom/MomJ
006669   STOCK Olfr17tm7Mom/MomJ
006570   STOCK Smn1tm1Msd Tg(Hlxb9-GFP)1Tmj Tg(SMN2)89Ahmb/J
007879   STOCK Stx1atm2Sud/J
005438   STOCK Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
006850   STOCK Tg(CAG-Bgeo,-NOTCH1,-EGFP)1Lbe/J
006876   STOCK Tg(CAG-Bgeo,-TEL/AML1,-EGFP)A6Lbe/J
003920   STOCK Tg(CAG-Bgeo/GFP)21Lbe/J
005441   STOCK Tg(CAG-DsRed*MST)1Nagy/J
003773   STOCK Tg(CAG-ECFP)CK6Nagy/J
003115   STOCK Tg(CAG-EGFP)B5Nagy/J
003116   STOCK Tg(CAG-EGFP)D4Nagy/J
005645   STOCK Tg(CAG-mRFP1)1F1Hadj/J
005105   STOCK Tg(Chx10-EGFP/cre-ALPP)2Clc/J
005854   STOCK Tg(Cp-EGFP)25Gaia/J
006334   STOCK Tg(Gad1-EGFP)94Agmo/J
006340   STOCK Tg(Gad1-EGFP)98Agmo/J
007896   STOCK Tg(Gt(ROSA)26Sor-EGFP)I1Able/J
005418   STOCK Tg(HIST1H2BB/EGFP)1Pa/J
006866   STOCK Tg(Ins1-DsRed*T4)32Hara/J
006784   STOCK Tg(Ins1-ECFP)24Hara/J
003658   STOCK Tg(TIE2GFP)287Sato/J
006129   STOCK Tg(Zp3-EGFP)1Dean/J
003274   STOCK Tg(tetNZL)2Bjd/J
005104   STOCK Tg(tetO-HIST1H2BJ/GFP)47Efu/J
005699   STOCK Tg(tetO-Ipf1,EGFP)956.6Macd/J
View Fluorescent Protein Strains     (139 strains)

Strains carrying other alleles of Tshr
000805   CBy.RF-Tshrhyt/J
View Strains carrying other alleles of Tshr     (1 strain)

Additional Web Information

Fluorescent Proteins/lacZ Systems

Research Applications

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

Developmental Biology Research
Skeletal Defects

Endocrine Deficiency Research
Adipose Defects
Thyroid Defects

Internal/Organ Research
Adipose Defects
Thyroid Defects

Metabolism Research

Mouse/Human Gene Homologs
hypothyroidism

Research Tools
Fluorescent Proteins
Metabolism Research

References

Selected Reference(s)

Marians RC; Ng L; Blair HC; Unger P; Graves PN; Davies TF. 2002. Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice. Proc Natl Acad Sci U S A 99(24):15776-81. [PubMed: 12432094]  [MGI Ref ID J:80513]

Additional References

Price and Supply Information

Strain Name: B6;129S1-Tshrtm1Rmar/J
Stock Number: 004858

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:

*Pricing for Shipping Destination selected:

        USA, Canada and Mexico

Price(s) in US dollars ($)
Cryorecovery Fee $1900.00
Cryopreserved Embryos Fee $1600.00

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to the Supply Notes for further information.
Supply Notes Cryopreserved Embryos
This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
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; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.

LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.
View Control Pricing Information for JAX® Strains.

General Terms and Conditions

View JAX® Mice & Services Conditions 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.
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

Go to JAX® Mice Query Form

(2.13)