Transthyretin Null Mice: Developmental Phenotypes

Transthyretin (TTR) is an extracellular thyroid hormone (TH) distributor protein. The TH distributor proteins ensure the adequate distribution of THs throughout the body, buffer against excess TH uptake into cells and maintain an extrathyroidal reserve of THs that may protect against TH deficiency when TH demand is increased. Thyroid hormones are vital for normal postnatal development. Thus, the postnatal development and growth of tissues responsive to THs has been investigated in TTR null mice. Although the developmental surge in plasma T4 concentrations was evident in 2-week-old TTR null mice, total and free T4 in the plasma were significantly reduced. Characteristics of the developing TTR null mice included delayed suckling-to-weaning transition, delayed onset of growth and retarded longitudinal bone growth. In addition, ileums from newborn TTR null mice displayed disordered cellular structure and contained fewer goblet cells. Although TH homeostasis within the brain of the developing TTR null mice did not appear to be compromised, subtle differences suggested a degree of immaturity in the developing brain, such as higher protein concentrations of cerebrospinal fluid from newborn and 2-week-old TTR null mice than in agematched wild type mice. Collectively, these studies demonstrate the importance of TTR during post-natal development and suggest that the development of the central nervous system is essentially preserved at the expense of peripheral tissues in TTR null mice.