PLASMA-CLEARANCE OF TRANSFERRIN IN CONTROL AND HYPOTRANSFERRINAEMIC MICE - IMPLICATIONS FOR REGULATION OF TRANSFERRIN TURNOVER

Kinetic studies were performed to determine the clearance of iodinated transferrin in hypotransferrinaemic mice, as compared to normal animals. Clearance of i.v. (and i.p.) administered radiolabelled protein in homozygous (hpx/hpx) mice was significantly faster than in heterozygous (hpx/+) and wild-type control (+/+) groups. A comparable t1/2 value for transferrin clearance in hpx/hpx mice was derived from a study in which immunoassay was performed on serum samples obtained at various times post-injection with normal mouse serum, indicating that: the clearance of I-125 reflected true clearance of transferrin protein. The clearance rate in the hpx/+ group was significantly slower than in +/+ mice. Calculation of transferrin synthesis rates in these two groups suggested that transferrin levels do not regulate transferrin synthesis rates, but may affect degradation; this observation is consistent with the fact: that transferrin levels in hpx/+ mice are > 50% of the values in +/+ mice, and indicates a partial compensation for reduced synthesis. The rapid clearance in hpx/hpx mice is an additional factor in determining the low levels of circulating transferrin in these synthesis-impaired mutants.