Description

Strain Information

Former Names B6;129-thyd/J    (Changed: 29-JUN-07 ) Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation +N1F1pN1

Development
The thyroid dyshormonogenesis mutation arose spontaneously in the B6.129-Tnfrsf1a^tm1Mak/J strain (stock #002818) at The Jackson Laboratory in 2000. After one backcross to C57BL/6J the offspring were intercrossed and the N1F2 progeny were genotyped for the Tnfrsf1a^tm1Mak mutation. Those lacking this targeted mutation were selected as breeders to continue the line, which has been maintained by breeding heterozygous males with hosts of homozygous ovarian transplantation. In 2007 this strain reached generation N1F6.

Control Information

	Control
	Heterozygote from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Thyroid Hormonogenesis, Genetic Defect In, 6 - 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

Duox2^thyd/Duox2^thyd

        B6(129)-Duox2^thyd/J

• endocrine/exocrine gland phenotype
• abnormal adenohypophysis morphology (MGI Ref ID J:121821)
  • although the posterior and intermediate lobes of the pituitary appear normal, the anterior pituitary gland is dysplastic and has many large abnormal cells, some with multiple nuclei
• abnormal thyroid follicle morphology (MGI Ref ID J:121821)
• decreased activity of thyroid (MGI Ref ID J:121821)
• thyroid gland hyperplasia (MGI Ref ID J:121821)
  • thyroid gland is highly dysplastic with few normal follicles and highly proliferating epithelial cells, which give rise to bilateral thyroid adenomas
• growth/size phenotype
• decreased body size (MGI Ref ID J:121821)
  • proportionally smaller than siblings
• decreased body weight (MGI Ref ID J:121821)
  • adults weigh approximately half that of littermate controls
• hearing/vestibular/ear phenotype
• abnormal tectorial membrane morphology (MGI Ref ID J:121821)
• decreased brainstem auditory evoked potential (MGI Ref ID J:121821)
  • ABR thresholds are on average 50-60 dB above those of heterozygous controls for all auditory test stimuli
• delayed inner ear development (MGI Ref ID J:121821)
  • at postnatal day 7 the epithelial cells that will form the inner sulcus of the organ of Corti are in a less-developed columnar form and still attached to a thickened tectorial membrane
  • at postnatal day 14 the organ of Corti resembles that of the postnatal day 7 control, but by 8 weeks of age development of the organ of Corti has progressed to appear nearly normal but with a variably thickened tectorial membrane
• homeostasis/metabolism phenotype
• decreased circulating insulin-like growth factor I level (MGI Ref ID J:121821)
  • at 8 weeks of age the average serum insulin-like growth factor level is 14.2 ng/ml versus 261 ng/ml in controls
• decreased circulating thyroxine level (MGI Ref ID J:121821)
  • at 8 weeks of age serum T4 levels are 10-fold lower than in heterzygous controls in both males and females
• increased circulating thyroid-stimulating hormone level (MGI Ref ID J:121821)
  • at 8 weeks of age TSH levels are 100 to 1000 fold higher than in sex-matched heterozygotes
• nervous system phenotype
• abnormal adenohypophysis morphology (MGI Ref ID J:121821)
  • although the posterior and intermediate lobes of the pituitary appear normal, the anterior pituitary gland is dysplastic and has many large abnormal cells, some with multiple nuclei
• reproductive system phenotype
• infertility (MGI Ref ID J:121821)
  • homozygotes do not breed
• skeleton phenotype
• *normal* skeleton phenotype (MGI Ref ID J:121821)
  • the growth plates appear normal
• decreased bone density (MGI Ref ID J:121821)
  • the whole skeleton appears under-mineralized with thin bones and narrow cortex
  • DEXA analysis at 8 weeks of age reveals that total body and areal bone mineral density is significantly reduced with no sex difference
• adipose tissue phenotype
• decreased percent body fat (MGI Ref ID J:121821)
  • DEXA analysis at 8 weeks of age shows decreased body fat relative to controls

View Research Applications

Research Applications

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

Endocrine Deficiency Research
Thyroid Defects

Mouse/Human Gene Homologs
hypothyroidism

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Duox2thyd
Allele Name		thyroid dyshormonogenesis
Allele Type		Spontaneous
Strain of Origin		B6.129-Tnfrsf1atm1Mak/J
Gene Symbol and Name		Duox2, dual oxidase 2
Chromosome		2
Gene Common Name(s)		A430065P05Rik; LNOX2; NOXEF2; P138-TOX; RIKEN cDNA A430065P05 gene; THOX2;
Molecular Note		A spontaneous C to T transition in exon 16 causes a change from a highly conserved valine to glycine at amino acid position 674. [MGI Ref ID J:121821]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Johnson KR; Marden CC; Ward-Bailey P; Gagnon LH; Bronson RT; Donahue LR. 2007. Congenital hypothyroidism dwarfism and hearing impairment caused by a missense mutation in the mouse dual oxidase 2 gene, Duox2 Mol Endocrinol 21(7):1593-602. [PubMed: 17440044]  [MGI Ref ID J:121821]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

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 Mouse Mutant Resource collection.

Control Information

	Control
	Heterozygote from the colony
	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

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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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

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