The Tgncog 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. Tgncog 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.)
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.
|Allele Name||congenital goiter|
|Allele Synonym(s)||Tgncog; cog|
|Gene Symbol and Name||Tg, thyroglobulin|
|Gene Synonym(s)||AITD3; TGN; Tgn; Tgn; cog; congenital goiter|
|Strain of Origin||AKR/J|
|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.|
|Carrier for Tg<cog>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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