micro-Crystallin as an intracellular 3,5,3'-triiodothyronine holder in vivo.
Previously, we identified reduced nicotinamide adenine dinucleotide phosphate-dependent cytosolic T(3) binding protein in rat cytosol. Cytosolic T(3)-binding protein is identical to mu-crystallin (CRYM). Recently, CRYM mutations were found in patients with nonsyndromic hereditary deafness. Although it has been established that CRYM plays pivotal roles in reserving and transporting T(3) into the nuclei in vitro and has a clinical impact on hearing ability, the precise functions of CRYM remain to be elucidated in vivo. To further investigate the in vivo functions of CRYM gene products, we have generated mice with targeted disruption of the CRYM gene, which abrogates the production of CRYM. CRYM knockout loses the reduced nicotinamide adenine dinucleotide phosphate-dependent T(3) binding activity in the cytosol of the brain, kidney, heart, and liver. At the euthyroid state, knockout significantly suppresses the serum concentration of T(3) and T(4) despite normal growth, heart rate, and hearing ability. The disruption of the gene does not alter the expression of TSHbeta mRNA in the pituitary gland or glutathione-S-transferase alpha2 and deiodinase 1 mRNAs in either the liver or kidney. When radiolabeled T(3) is injected intravenously, labeled T(3) rapidly enters into and then escapes from the tissues in CRYM-knockout mice. These data suggest that because of rapid T(3) turnover, disruption of the CRYM gene decreases T(3) concentrations in tissues and serum without alteration of peripheral T(3) action in vivo.
Suzuki
Satoru
S
Department of Aging Medicine and Geriatrics, Institute on Aging and Adaptation, Shinshu University, Graduate School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan. soutaro@hsp.md.shinshu-u.ac.jp
Suzuki
Nobuyoshi
N
Mori
Jun-Ichirou
J
Oshima
Aki
A
Usami
Shinichi
S
Hashizume
Kiyoshi
K
D000818:Animals; D003459:Crystallins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006309:Hearing / Q000235:genetics; D006339:Heart Rate / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D037322:Thyrotropin, beta Subunit / Q000235:genetics / Q000378:metabolism; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000378:metabolism*; D000090803:mu-Crystallins
C000716470:Crym protein, mouse; C000716471:Crym protein, rat; D003459:Crystallins; D007527:Isoenzymes; D012333:RNA, Messenger; D037322:Thyrotropin, beta Subunit; D014284:Triiodothyronine; D009249:NADP; D014285:Triiodothyronine, Reverse; D007453:Iodide Peroxidase; D000090803:mu-Crystallins; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D013974:Thyroxine