Immunohistochemical analysis of transferrin receptor: regional and cellular distribution in the hypotransferrinemic (hpx) mouse brain

The hypotransferrinemic (hpx) mouse mutant produces < 1% of the normal circulating level of transferrin (Tf). Heterozygote animals of this strain (hpx / +) have approximately 50% of normal plasma Tf levels. in this study we examine the cellular and regional distribution of Tf receptor (Tf-R) in the brain of wild type, hpx / + and mutant (hpx/hpx) mice. Also, using slot-blot (immunoblot) analysis, we describe the relative amount of Tf-R in brain microvessels of hpx / + animals compared with wild type. Tf-R was seen primarily in neurons throughout the brains of wild type, hpx / + and hpx/hpx animals. Gray matter areas immunoreacted more robustly than white matter areas. Oligodendrocytes and third ventricle tanycytes, both of which we have previously described as iron-positive, did not immunoreact for Tf-R. Tf-R immunohistochemical reaction in wild type, hpx / + and hpx/hpx brains appeared similar. Immunoblot analysis of isolated cortical microvessels from wild type and hpx / + animals revealed no upregulation of Tf-R expression in hpx / + (relative to normal) despite a 50% decrease in circulating Tf levels. These results indicate that Tf-R is primarily expressed by neurons and that half normal levels of Tf (hpx / +) or transferrin supplementation (hpx/hpx) are apparently sufficient for normal expression and distribution of Tf-R. Because of the lack of circulating Tf, but unaltered Tf-R expression, hpx mice could serve as a model for delivery of therapeutic agents via the Tf/Tf-R system. (C) 1998 Elsevier Science B.V. All rights reserved.