474. Reelin, a protein regulating neural development, is expressed in the blood in adult mammals

Abstract

Reelin is a regulatory protein for telencephalic and cerebellar lamination during development and is expressed in several structures in the adult brain. However, only trace amounts have previously been reported in peripheral tissues. Since reelin structurally resembles extracellular matrix proteins, and since many matrix proteins have been detected in blood, we hypothesized that reelin might also be detectable in the circulation. Reelin (420 kDa) and two smaller reelin-immunoreactive bands (310 and 160 kDa) were readily observed in serum and platelet-poor plasma of rats, wild-type mice and humans, but were not detectable in homozygous reeler (rl −/−) mice. Plasma levels of reelin were reduced by half in heterozygous reeler (rl +/−) mice. Western blotting and immunocytochemistry using anti-reelin monoclonal antibodies indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the adrenal medulla, and in a subset of cells co-expressing α-melanocyte stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary in rats failed to decrease the amount of full-length (420 kDa) reelin expressed in serum. Adult liver expressed an amount of reelin mRNA that is 1/3 of that expressed in cerebral cortex of the adult mouse; full-length reelin protein was detectable in liver extracts in situ and acutely isolated liver cells secreted full-length reelin in vitro. Given its size, liver may play a major role in producing the pool of circulating reelin. It now becomes feasible to study the regulation of reelin gene expression in an accessible bodily fluid in living humans.