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.
Dickinson
T K
TK
Division of Natural Sciences, Keuka College, Keuka Park, NY 14478, USA.
Connor
J R
JR
D000818:Animals; D001921:Brain / Q000166:cytology*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology; D006720:Homozygote; D007150:Immunohistochemistry; D007501:Iron / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009928:Organ Specificity; D011990:Receptors, Transferrin / Q000032:analysis*; D014168:Transferrin / Q000032:analysis / Q000172:deficiency* / Q000235:genetics
D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron