Hishinuma_2000_Endocrinology_141_4050

Reference

Title : A novel missense mutation (G2320R) in thyroglobulin causes hypothyroidism in rdw rats - Hishinuma_2000_Endocrinology_141_4050
Author(s) : Hishinuma A , Furudate S , Oh-Ishi M , Nagakubo N , Namatame T , Ieiri T
Ref : Endocrinology , 141 :4050 , 2000
Abstract :

The rdw rat is a hereditary hypothyroid variant initially derived from the Wistar-Imamichi strain. Proteome analysis by two-dimensional gelelectrophoresis showed that molecular chaperones accumulated in the thyroid glands, suggesting retention of abnormal proteins in the endoplasmic reticulum (ER). Anatomical studies indicated that thyroglobulin (Tg) was not secreted into the follicular lumina, but retained in the dilated ER. Sequencing of the entire Tg complementary DNA from the rdw rat revealed a missense mutation (G2320R) in the acetylcholinesterase-like domain at the 2320th amino acid residue. Carbohydrate residues of the G2320R Tg mutant were of the high-mannose ER type, as shown by sensitivity to the treatment with endoglycosidase H. Molecular chaperones, GRP94, GRP78, and calreticulin, were all accumulated in the rdw rat thyroid glands. Computer analysis of protein secondary structure predicted that the mutation would cause extension of the helix where beta-sheet and turns were formed in the normal Tg. Altered folding of Tg might account for the impaired intracellular transport of Tg and activated premature degradation by the same mechanism as in ER storage diseases.

PubMedSearch : Hishinuma_2000_Endocrinology_141_4050
PubMedID: 11089535
Gene_locus related to this paper: ratno-thyro

Related information

Mutation G2320R_ratno-thyro
Gene_locus ratno-thyro

Citations formats

Hishinuma A, Furudate S, Oh-Ishi M, Nagakubo N, Namatame T, Ieiri T (2000)
A novel missense mutation (G2320R) in thyroglobulin causes hypothyroidism in rdw rats
Endocrinology 141 :4050

Hishinuma A, Furudate S, Oh-Ishi M, Nagakubo N, Namatame T, Ieiri T (2000)
Endocrinology 141 :4050