Description

Strain Information

Former Names CBy.AK-Tgncog/J    (Changed: 19-OCT-06 ) Type Congenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain BALB/cBy Generation N10F42pN1

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

Description
The Tg^cog mutation causes the development of goiters due to failed processing of thyroglobulin. Homozygotes are smaller in overall size by 15 days of age. They display an increase in growth rate at the time of weaning but generally do not attain comparable size with their wildtype littermates. Increased thyroidal volume is apparent at embryonic day 18, and continues enlarging to an average of 5 fold higher than normal at 8 weeks of age and 20 fold normal at 10 months of age. In addition to decreased serum T3 and T4 levels, homozygotes have increased serum thyroid stimulating hormone levels, reduced levels of serum IGFBP-3, IGFBP-4, and IGFBP-2, mild anemia, and hypomyelination restricted to the cerebrum. Tg^cog is an outwardly recessive mutation, but microdissection reveals a heterozygous phenotype as well. Thyrofollicular cells of heterozygotes have swollen protein-containing vesicles similar to but more moderate than those found in homozygotes. Thyroid extracts from homozygotes have an increased percent of protein and heterozygotes have an intermediate percent of protein relative to wild type siblings. (Beamer et al., 1987; Adkison et al., 1990; Sugisaki et al., 1991, 1992, and 1993; Kim et al., 1996 and1998.)

Development
The cog allele of Tg arose spontaneously in the AKR/J strain (then at F131) at The Jackson Laboratory. The mutation was maintained via sibling mating for 9 generations then backcrossed once to AKR/J then sibling mated for 4 generations before being backcrossed to BALB/cBy. A single male at N1F4 was bred to a BALB/cBy female, their heterozygous offspring sibling mated to generate a homozygous N1F1 female that was backcrossed to a BALB/cBy male. Their heterozygous N2 offspring were sibling mated to generate a homozygous male that was backcrossed to a BALB/cBy female. The backcross-intercross breeding scheme was continued from this point on using female BALB/cBy and male homozygotes in the backcross generations until the congenic strain reached N10. This strain has been maintained via sibling mating primarily homozygote x heterozygote or vice versa since N10. In 2002 it was at N10F33.

Control Information

	Control
	Heterozygote from the colony
	001026 BALB/cByJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Tg^cog allele

002549

STOCK Tgcog/J

View Strains carrying   Tg^cog     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Tg^cog/Tg^cog

        AKR/J

• endocrine/exocrine gland phenotype
• enlarged thyroid gland (MGI Ref ID J:13923)
  • reduced when diet supplemented with desiccated thyroid powder
  • hypertrophy and hyperplasia of thyrofollicular cells
  • obliteration of most follicular lumens
  • small numbers of lymphocytes in degenerating follicles
• growth/size phenotype
• disproportionate dwarf (MGI Ref ID J:13923)
  • evident at day 15 postnatal
  • repaired when diet supplemented with desiccated thyroid powder
• increased growth rate (MGI Ref ID J:13923)
  • evident between 4 and 7 weeks of age
• homeostasis/metabolism phenotype
• decreased circulating thyroxine level (MGI Ref ID J:13923)

Tg^cog/Tg^cog

        involves: AKR/J * C57BL/6By

• endocrine/exocrine gland phenotype
• enlarged thyroid gland (MGI Ref ID J:8567)
  • hypertrophy of thyrofollicular cells
• growth/size phenotype
• decreased body weight (MGI Ref ID J:8567)
  • evident by 15 days postnatal
  • repaired when diet at weaning was supplemented with desiccated thyroid powder
  • evident at day 15 postnatal
• hematopoietic system phenotype
• anemia (MGI Ref ID J:8567)
• decreased hematocrit (MGI Ref ID J:8567)
• homeostasis/metabolism phenotype
• decreased circulating thyroxine level (MGI Ref ID J:8567)
• decreased circulating triiodothyronine level (MGI Ref ID J:8567)
• increased circulating thyroid-stimulating hormone level (MGI Ref ID J:8567)
• nervous system phenotype
• abnormal myelination (MGI Ref ID J:3079)
  • hypomyelination, restricted to cerebrum
• decreased brain weight (MGI Ref ID J:3079)
  • cerebrum and cerebellum weighed significantly less than littermate controls
  • brain stem weight equivalent to littermate controls

View Research Applications

Research Applications

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

Tg^cog related

Cell Biology Research
Post-translational Processing
Protein Processing

Endocrine Deficiency Research
Thyroid Defects

Internal/Organ Research
Thyroid Defects

Mouse/Human Gene Homologs
congenital goiter with hypothyroidism

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tgcog
Allele Name		congenital goiter
Allele Type		Spontaneous
Common Name(s)		Tgncog; cog;
Strain of Origin		AKR/J
Gene Symbol and Name		Tg, thyroglobulin
Chromosome		15
Gene Common Name(s)		AITD3; TGN; Tgn; cog; congenital goiter;
Molecular Note		The mutation is a C to T transition yielding a leucine to proline change at residue 2263. This falls within the acetylcholinesterase domain and impacts protein conformation. This conformational mutation is temperature sensitive; there is an increase in the level of TGN secreted from mutant thyrocytes at 31 degrees relative to the level secreted at 37 degrees, which is below the threshold of detection by PAGE. A small amount of functional TGN is processed in homozygous mice and serum triiodothyroinine and tetraiodothyroinine are found, albeit at vastly reduced levels. [MGI Ref ID J:49474]

Genotyping

Genotyping Information

Genotyping Protocols

Tg^cog, PYRO, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Beamer WG; Maltais LJ; DeBaets MH; Eicher EM. 1987. Inherited congenital goiter in mice. Endocrinology 120(2):838-40. [PubMed: 3803305]  [MGI Ref ID J:8567]

Additional References

Adkison LR; Taylor S; Beamer WG. 1990. Mutant gene-induced disorders of structure, function and thyroglobulin synthesis in congenital goitre (cog/cog) in mice. J Endocrinol 126(1):51-8. [PubMed: 1696305]  [MGI Ref ID J:46324]

Mayerhofer A; Amador AG; Beamer WG; Bartke A. 1988. Ultrastructural aspects of the goiter in cog/cog mice. J Hered 79(3):200-3. [PubMed: 3392390]  [MGI Ref ID J:24038]

Sugisaki T; Beamer WG; Noguchi T. 1992. Microcephalic cerebrum with hypomyelination in the congenital goiter mouse (cog). Neurochem Res 17(10):1037-40. [PubMed: 1508304]  [MGI Ref ID J:3079]

Tg^cog related

Beamer WG; Coleman DL. 1982. [Adipose storage deficiency (asd)]. Mouse News Lett 67:21.  [MGI Ref ID J:13923]

Kim PS; Hossain SA; Park YN; Lee I; Yoo SE; Arvan P. 1998. A single amino acid change in the acetylcholinesterase-like domain of thyroglobulin causes congenital goiter with hypothyroidism in the cog/cog mouse: a model of human endoplasmic reticulum storage diseases. Proc Natl Acad Sci U S A 95(17):9909-13. [PubMed: 9707574]  [MGI Ref ID J:49474]

Sugisaki T; Beamer WG; Noguchi T. 1992. Microcephalic cerebrum with hypomyelination in the congenital goiter mouse (cog). Neurochem Res 17(10):1037-40. [PubMed: 1508304]  [MGI Ref ID J:3079]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	Homozygotes may need to be left with its mother until 4 or 5 weeks of age as they are small. This strain can be bred homozygote x heterozygote, but homozygous males are better breeders than homozygous females.

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 of Strains Needing Progeny Testing. 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 untested males and two untested females (two pairs) will be recovered, 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 overall recovery time to approximately 25 weeks. However, all pups recovered will be sent. Progeny testing is required to identify the genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. We can perform the progeny testing for you as a service or we can ship all recovered animals (at least two untested pairs) to you for progeny testing at your facility. If you perform the progeny testing, there is NO guarantee that a carrier will be identified. If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female (one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the time taken to produce the mice identified as carrying the mutation. Please note that identified 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. Please contact Customer Service for more information on the cost of progeny testing for a strain: Tel: 1-800-422-6423 or 1-207-288-5845. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Heterozygote from the colony
	001026 BALB/cByJ
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.

---

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.