μ-Crystallin as an Intracellular 3,5,3′-Triiodothyronine Holder in Vivo

Previously, we identified reduced nicotinamide adenine dinucleotide phosphate-dependent cytosolic T3 binding protein in rat cytosol. Cytosolic T3-binding protein is identical to μ-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 T3 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 T3 binding activity in the cytosol of the brain, kidney, heart, and liver. At the euthyroid state, knockout significantly suppresses the serum concentration of T3 and T4 despite normal growth, heart rate, and hearing ability. The disruption of the gene does not alter the expression of TSHβ mRNA in the pituitary gland or glutathione-S-transferase α2 and deiodinase 1 mRNAs in either the liver or kidney. When radiolabeled T3 is injected intravenously, labeled T3 rapidly enters into and then escapes from the tissues in CRYM-knockout mice. These data suggest that because of rapid T3 turnover, disruption of the CRYM gene decreases T3 concentrations in tissues and serum without alteration of peripheral T3 action in vivo.