Delayed development of specific thyroid hormone-regulated events in transthyretin null mice

Monk JA, Sims NA, Dziegielewska KM, Weiss RE, Ramsay RG, Richardson SJ. Delayed development of specific thyroid hormone-regulated events in transthyretin null mice. Am J Physiol Endocrinol Metab 304: E23-E31, 2013. First published October 23, 2012; doi:10.1152/ajpendo.00216.2012.-Thyroid hormones (THs) are vital for normal postnatal development. Extracellular TH distributor proteins create an intravascular reservoir of THs. Transthyretin (TTR) is a TH distributor protein in the circulatory system and is the only TH distributor protein synthesized in the central nervous system. We investigated the phenotype of TTR null mice during development. Total and free 3', 5', 3,5-tetraiodo-L-thyronine (T-4) and free 3', 3,5-triiodo-L-thyronine (T-3) in plasma were significantly reduced in 14-day-old (P14) TTR null mice. TTR null mice also displayed a delayed suckling-to-weaning transition, decreased muscle mass, delayed growth, and retarded longitudinal bone growth. In addition, ileums from postnatal day 0 (P0) TTR null mice displayed disordered architecture and contained fewer goblet cells than wild type. Protein concentrations in cerebrospinal fluid from P0 and P14 TTR null mice were higher than in age-matched wild-type mice. In contrast to the current literature based on analyses of adult TTR null mice, our results demonstrate that TTR has an important and nonredundant role in influencing the development of several organs.