Expression of a thyroglobulin (Tg) variant in mouse kidney glomerulus.
Thyroglobulin (Tg) is an essential substrate for thyroid hormone biosynthesis whose production is primarily limited to the thyroid follicular cell. We have previously identified an approximately 1.2 kb fragment of Tg mRNA in cultured mouse mesangial cells, and in the present study provide evidence showing that this transcript is transcribed and translated into a unique protein (kTg) in the kidney, but not the thyroid gland. Cloning of kTg from a mouse kidney cDNA library showed that transcription starts in the middle of intron 41 of the Tg gene and continues in-frame with the remaining coding sequence of thyroid-derived Tg beginning with exon 42. Translation of this mRNA is predicted to yield a protein of 367 amino acids (40 kDa) containing a unique 13 amino acid sequence serving as a signal peptide followed by a 354 amino acid segment identical to the carboxy-terminal end of thyroid Tg. Western blot analysis with an antibody directed against the C-terminus of thyroid Tg detected a 40 kDa protein expressed in the kidney. Immunohistochemistry with this antibody showed that immunoreactive Tg was localized in podocytes and the mesangial area of the renal glomerulus. A part of a homologous transcript was also detected in human kidney, and the kTg protein was recognized by sera from Hashimoto's thyroiditis but not from controls. Together these results suggest that a unique low molecular weight variant of Tg is expressed in the kidney, where it could serve both physiological and pathological roles, including that of an autoantigen.
Wu
Huhehasi
H
Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan.
Suzuki
Sayuri
S
Sellitti
Donald F
DF
Doi
Sonia Q
SQ
Tanigawa
Kazunari
K
Aizawa
Sayaka
S
Akama
Takeshi
T
Kawashima
Akira
A
Mishima
Masayo
M
Ishii
Norihisa
N
Yoshida
Akio
A
Hisatome
Ichiro
I
Koles
Nancy L
NL
Katoh
Ryohei
R
Suzuki
Koichi
K
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D003001:Cloning, Molecular; D015723:Gene Library; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology*
D001324:Autoantigens; D013954:Thyroglobulin