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Department of Physics, School of Science (M.O., T.M.), and Department of Laboratory Animal Science, School of Medicine (S.F.), Kitasato University, 1–15-1 Kitasato, Sagamihara-shi, Kanagawa 228, Japan; Laboratory of Biopolymer Conformation Analysis, Mitsubishi Kasei Institute of Life Sciences (A.O.), 11 Minamiooya, Machida-shi, Tokyo 194, Japan; and Institute for Experimental Animal Science, Nagoya City University Medical School (J.-Y.K., T.A.), Mizuho-ku, Nagoya-shi, Aichi 467, Japan
Address all correspondence and requests for reprints to: Masamichi Oh-Ishi, Ph.D., Kitasato University School of Science, 1–15-1 Kitasato, Sagamihara-shi, 228 Japan.
Proteins having relations to hereditary dwarfism of the rdw rat (gene symbol: rdw) were searched for in various tissues of the rat with an improved two-dimensional gel electrophoresis technique followed by immunoblotting and microsequencing. Tissues inspected were cerebral cortex, cerebellum, brain trunk, hypothalamus, pituitary, thyroid gland, liver, testis, spleen, and thymus. Only pituitary and thyroid glands among those tissues showed abnormalities in protein contents. GH and PRL contents in the rdw pituitary were much less than in the normal one, which in the former were 1/15 and less than 1/30 times as much as in the latter, respectively, but the abnormalities in the rdw thyroid were far more serious than in the pituitary. At least 18 protein levels in the rdw thyroid were above, and 17 were below the normal. Those identified among the increased proteins were endoplasmin (GRP94), immunoglobulin heavy chain binding protein (BiP/GRP78), and heat shock protein 70 (hsp70), the contents of which respectively were 40 times, 10 times and more than 50 times as much in the rdw thyroid as in the normal tissue. Because BiP and endoplasmin are known to be ER resident proteins, and because all three belong to a chaperone protein family, accumulation of these proteins in the rdw thyroid suggests that protein folding and secreting disorders underlie the hypothyroidism of the rdw rat.
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