Loading Mouse GIF
Loading...

Strain Name:
NOD.Cg-H2h4 Tg(TG-TSHR)51.9Smcl/Mmmh
Stock Number:
037586-MU
Citation ID:
RRID:MMRRC_037586-MU
Other Names:
hTSHR/NOD-H2h4 mice, TSHR-NOD-Lo

Strain Information

H2h4
Name: histocompatibility-2, MHC; h4 variant
Synonyms: H-2h4
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 17
Alteration at locus: Targeted Mutation
Tg
Name: thyroglobulin
Synonyms: Tgn
Type: Gene
Species: Mouse
Chromosome: 15
Alteration at locus: Targeted Mutation
NCBI: 21819
Homologene: 2430
Tshr
Name: thyroid stimulating hormone receptor
Synonyms: hyt, pet, hypothroid
Type: Gene
Species: Mouse
Chromosome: 12
Alteration at locus: Targeted Mutation
NCBI: 22095
Homologene: 315
Tg(TG-TSHR)51.9Smcl
Name: transgene insertion 51.9, Sandra M McLachlan
Synonyms: pTg-h-A-subunit, tgic, A-subunit transgenic
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
Human TSHR A-subunit targeted to (and expressed in) the thyroid gland by the bovine thyroglobulin promoter. The original transgenics were generated in BALB/c and have been backcrossed to NOD.H2h4.
Genotype Determination
Phenotype

Homozygous: Not studied

Hemizygous: Undetermined

These mice spontaneously produce pathogenic TSHR antibodies which are the direct cause of Graves’ disease in humans. 

Mammalian Phenotype Terms
Allelic Composition: H2h4/H2h4 (Genetic Background: NOD.Cg-H2h4 )

Allelic Composition: H2h4/H2g7 (Genetic Background: NOD.Cg-H2h4 )

MeSH Terms
  • Adenoviridae/genetics
  • Amino Acid Sequence
  • Animals
  • Autoantibodies/immunology
  • Autoantigens/immunology
  • Autoimmunity
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Vectors
  • Graves Disease/immunology
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Protein Subunits/immunology
  • Receptors, Thyrotropin/biosynthesis
  • Receptors, Thyrotropin/genetics
  • Receptors, Thyrotropin/immunology
  • Sequence Homology, Amino Acid
  • Thyroid Gland/immunology
  • Thyroid Gland/pathology
  • Graves Disease/pathology
  • Hashimoto Disease/immunology
  • Hashimoto Disease/pathology
  • Hyperthyroidism/immunology
  • Hyperthyroidism/pathology
  • Immunization
  • Immunoglobulins, Thyroid-Stimulating/metabolism
  • Immunohistochemistry
  • T-Lymphocytes, Regulatory/immunology
  • T-Lymphocytes, Regulatory/metabolism
  • Thyroid Gland/metabolism
  • Animals, Zoo
  • Autoantibodies/blood
  • Female
  • Hominidae
  • Hypothyroidism/immunology
  • Hypothyroidism/pathology
  • Hypothyroidism/veterinary
  • Iodide Peroxidase/immunology
  • Lymphocytes
  • Male
  • Species Specificity
  • Thyroglobulin/immunology
  • Thyroid Gland/cytology
  • Thyroxine/blood
  • Triiodothyronine/blood
Strain Development
1) This strain carries the same mutation as C.Cg-Tg(TG-TSHR)51.9Smcl/Mmucd, MMRRC:014125 mice that express the human thyrotropin receptor (TSHR) A-subunit at low levels in the thyroid gland (1,2). This strain is on the BALB/c background. Males of this strain were bred to female NOD.H2h4 mice [NOD.Cg-H2h4/DilTacUmmJ to generate N1. 3) Male N1 offspring bearing the “51.9" transgene were backcrossed to female NOD.H2h4 mice to generate N2. 4)To introduce the NOD.H2h4 Y chromosome, N4 positive females were crossed to NOD.H2h4 males. Thereafter, male transgenics were bred to NOD.H2h4 females. 5) Males with the highest percentage of NOD.H2h4 genes (analyzed by Jackson Labs) were used when possible (sometimes the “best” male was aggressive and could not be used for breeding). At N6, three males had 99% NOD.H2h4 genes and we used for breeding. 6) We are currently generating N10 mice. The offspring will be heterozygous and will be maintained by crossing male transgenics to NOD.H2h4 females. Offspring from these crosses (from N2 to N8) “hTSHR/NOD-H2h4 mice” spontaneously produce pathogenic TSHR antibodies which are the direct cause of Graves’ disease in humans. Notes: Graves’ disease is one of the commonest autoimmune diseases in humans; approximately 1% of the population will develop Graves’ disease in their lifetime. No animals other than humans generate TSHR antibodies spontaneously, not even our closest relatives the great apes (3). Consequently, this transgenic mouse is the first animal model that spontaneously produces TSHR antibodies and can be investigated for novel immune approaches to suppress TSHR antibody production with the potential to develop novel therapies to cure Graves’ disease in humans. Our data were presented as one of four selected “Highlighted Orals” at the 84th Annual Meeting of the American Thyroid Association on October 30 in San Diego (4). References 1. Pichurin, P. N., C.-R. Chen, G. D. Chazenbalk, H. Aliesky, N. Pham, B. Rapoport, and S. M. McLachlan. 2006. Targeted expression of the human thyrotropin receptor A-subunit to the mouse thyroid: Insight into overcoming the lack of response to A-subunit adenovirus immunization. J Immunol. 176:668-676. 2. McLachlan, S. M., Y. Nagayama, P. N. Pichurin, Y. Mizutori, C. R. Chen, A. Misharin, H. A. Aliesky, and B. Rapoport. 2007. The link between Graves' disease and Hashimoto's thyroiditis: A role for regulatory T cells. Endocrinol. 148:5724-5733. 3. Aliesky, H., C. L. Courtney, B. Rapoport, and S. M. McLachlan. 2013. Thyroid autoantibodies are rare in nonhuman great apes and hypothyroidism cannot be attributed to thyroid autoimmunity. Endocrinol. 154:4896-4907. 4. McLachlan, S. M., Aliesky, H., Banuelos, B., and Rapoport, B. 2014. Development of a unique mouse model for Graves' disease that spontaneously develops pathogenic TSH receptor antibodies. 84th Annual Meeting of the American Thyroid Association October 29-November 2, 2014 , 87. 2014 (Abstract)
Suggested Control Mice
Wild-type littermates
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.
  • Immunology and Inflammation
  • Models for Human Disease
    • Graves’ disease
Donor
Sandra M McLachlan, Ph.D., Cedars-Sinai Medical Center & University of California, Los Angeles.
Primary Reference

McLachlan SM, Aliesky H, Banuelos B, and Rapoport B. Development of a unique mouse model for Graves' disease that spontaneously develops pathogenic TSH receptor antibodies. 84th Annual Meeting of the American Thyroid Association October 29-November 2, 2014 , 87. 2014 (presentation)
Pichurin PN, Chen CR, Chazenbalk GD, Aliesky H, Pham N, Rapoport B, and McLachlan SM. Targeted expression of the human thyrotropin receptor A-subunit to the mouse thyroid: Insight into overcoming the lack of response to A-subunit adenovirus immunization. J Immunol. 2006 Jan 1;176(1):668-76. (Medline PMID:16365463)
McLachlan SM, Nagayama Y, Pichurin PN, Mizutori Y, Chen CR, Misharin A, Aliesky HA, and Rapoport B. The link between Graves' disease and Hashimoto's thyroiditis: A role for regulatory T cells. Endocrinology. 2007 Dec;148(12):5724-33. Epub 2007 Sep 6.
(Medline PMID:17823263)

Aliesky H, Courtney CL, Rapoport B, and McLachlan SM. Thyroid autoantibodies are rare in nonhuman great apes and hypothyroidism cannot be attributed to thyroid autoimmunity. Endocrinology. 2013 Dec;154(12):4896-907. Epub 2013 Oct 3. (Medline PMID:24092641)

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.
Coat Color
White
MMRRC Breeding System
Backcross
Breeding Scheme(s)
  • Wild-type (NOD.H2h4) female x Hemizygous male or reciprocal mating
Generation
N10
Overall Breeding Performance
Good
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined Undetermined
Homozygotes are fertile: Undetermined Undetermined
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: 6 months 8 months
Average litter size
4-6
Recommended wean age
3 weeks

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
037586-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
037586-MU-RESUS Litter recovered from cryo-archive $2,697.00 / $5,488.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.