The Tgn^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 have 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. Tgn^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 congenital goiter mutation arose spontaneously in the AKR/J strain (then at generation 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 was then maintained via sibling mating and in 1995 homozygous males at generation N10F21 were bred with C57BL/6J females to generate embryos for cryopreservation.

Selected References

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

View All References

Genetics

Tg^cog

Allele Symbol: Tg^cog

Allele Name	congenital goiter
Allele Type	Spontaneous
Allele Synonym(s)	cog; Tgn^cog
Gene Symbol and Name	Tg, thyroglobulin
Gene Synonym(s)
Strain of Origin	AKR/J
Chromosome	15
Molecular Note	The mutation is a T-to-C transition at coding nucleotide 6848 (c.6848T>C) yielding a leucine to proline change at positionn 2283 (p.L2283P). 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.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

congenital hypothyroidism

Research Areas By Phenotype

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

Genotype: Tg^cog related

Endocrine Deficiency Research
- Thyroid Defects
Internal/Organ Research
- Thyroid Defects
Cell Biology Research
- Post-translational Processing
- Protein Processing
Mouse/Human Gene Homologs
- congenital goiter with hypothyroidism

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg^cog/Tg^cog
AKR/J-Tg

endocrine/exocrine gland phenotype

abnormal thyroid follicle morphology
- obliteration of most follicular lumens
- small numbers of lymphocytes in degenerating follicles

abnormal thyroid follicular cell morphology
- hypertrophy and hyperplasia of thyrofollicular cells

enlarged thyroid gland
- reduced when diet supplemented with desiccated thyroid powder

growth/size/body region phenotype

disproportionate dwarf
- evident at day 15 postnatal
- repaired when diet supplemented with desiccated thyroid powder

increased growth rate
- evident between 4 and 7 weeks of age

homeostasis/metabolism phenotype

decreased circulating thyroxine level
- serum thyroxine is significantly reduced

Genotype: Tg^cog/Tg^cog
involves: AKR/J * C57BL/6By

endocrine/exocrine gland phenotype

enlarged thyroid gland
- hypertrophy of thyrofollicular cells

nervous system phenotype

abnormal myelination
- hypomyelination, restricted to cerebrum

decreased brain weight
- brain stem weight equivalent to littermate controls
- cerebrum and cerebellum weighed significantly less than littermate controls

growth/size/body region phenotype

decreased body weight
- evident at day 15 postnatal
- evident by 15 days postnatal
- repaired when diet at weaning was supplemented with desiccated thyroid powder

hematopoietic system phenotype

anemia

decreased hematocrit

homeostasis/metabolism phenotype

decreased circulating thyroxine level

decreased circulating triiodothyronine level

increased circulating thyroid-stimulating hormone level

References

Beamer WG; Maltais LJ; DeBaets MH; Eicher EM. 1987. Inherited congenital goiter in mice. Endocrinology 120(2):838-40PubMed: 3803305 MGI: 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):51-8PubMed: 1696305 MGI: J:46324
Mayerhofer A; Amador AG; Beamer WG; Bartke A. 1988. Ultrastructural aspects of the goiter in cog/cog mice. J Hered 79(3):200-3PubMed: 3392390 MGI: J:24038
Sugisaki T; Beamer WG; Noguchi T. 1992. Microcephalic cerebrum with hypomyelination in the congenital goiter mouse (cog). Neurochem Res 17(10):1037-40PubMed: 1508304 MGI: J:3079

Additional - Tg^cog related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the congenital goiter mouse strain in a publication, please cite the originating article(s) and include JAX stock #002549 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Carrier for Tg<cog>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES 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 JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or SERVICES by JACKSON.

Also Known As:congenital goiter

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Tgcog

Allele Symbol: Tgcog

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Tgcog related

Mammalian Phenotype Terms by Genotype

Genotype: Tgcog/TgcogAKR/J-Tg

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Tgcog/Tgcoginvolves: AKR/J * C57BL/6By

endocrine/exocrine gland phenotype

nervous system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Tgcog related

Genotyping Protocols

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tg^cog

Allele Symbol: Tg^cog

Genotype: Tg^cog related

Genotype: Tg^cog/Tg^cog
AKR/J-Tg

Genotype: Tg^cog/Tg^cog
involves: AKR/J * C57BL/6By

Additional - Tg^cog related