| RRC ID |
33267
|
| 著者 |
Sato A, Abe K, Yuzuriha M, Fujii S, Takahashi N, Hojo H, Teramoto S, Aoyama H.
|
| タイトル |
A novel mutation in the thyroglobulin gene that causes goiter and dwarfism in Wistar Hannover GALAS rats.
|
| ジャーナル |
Mutat Res
|
| Abstract |
Outbred stocks of rats have been used extensively in biomedical, pharmaceutical and/or toxicological studies as a model of genetically heterogeneous human populations. One of such stocks is the Wistar Hannover GALAS rat. However, the colony of Wistar Hannover GALAS rat has been suspected of keeping a problematic mutation that manifests two distinct spontaneous abnormalities, goiter and dwarfism, which often confuses study results. We have successfully identified the responsible mutation, a guanine to thymine transversion at the acceptor site (3' end) of intron 6 in the thyroglobulin (Tg) gene (Tgc.749-1G>T), that induces a complete missing of exon 7 from the whole Tg transcript by mating experiments and subsequent molecular analyses. The following observations confirmed that Tgc.749-1G>T/Tgc.749-1G>T homozygotes manifested both dwarfism and goiter, while Tgc.749-1G>T/+ heterozygotes had only a goiter with normal appearance, suggesting that the mutant phenotypes inherit as an autosomal semi-dominant trait. The mutant phenotypes, goiter and dwarfism, mimicked those caused by typical endocrine disrupters attacking the thyroid. Hence a simple and reliable diagnostic methodology has been developed for genomic DNA-based genotyping of animals. The diagnostic methodology reported here would allow users of Wistar Hannover GALAS rats to evaluate their study results precisely by carefully interpreting the data obtained from Tgc.749-1G>T/+ heterozygotes having externally undetectable thyroidal lesions.
|
| 巻・号 |
762
|
| ページ |
17-23
|
| 公開日 |
2014-4-1
|
| DOI |
10.1016/j.mrfmmm.2014.02.003
|
| PII |
S0027-5107(14)00026-8
|
| PMID |
24582622
|
| MeSH |
Animals
Animals, Outbred Strains
Base Sequence
Dicofol / toxicity
Dwarfism / genetics*
Dwarfism / metabolism
Dwarfism / pathology
Endocrine Disruptors / toxicity
Exons
Female
Gene Expression
Goiter / genetics*
Goiter / metabolism
Goiter / pathology
Heterozygote
Homozygote
Introns
Male
Molecular Sequence Data
Mutation*
RNA Splicing*
Rats
Rats, Wistar
Thyroglobulin / genetics*
Thyroglobulin / metabolism
Thyroid Gland / drug effects
Thyroid Gland / metabolism
Thyroid Gland / pathology
|
| IF |
2.463
|
| 引用数 |
5
|
|
WOS 分野
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
TOXICOLOGY
GENETICS & HEREDITY
|
| リソース情報 |
| ラット |
DWH/let |
