DEVELOPMENTAL AND TISSUE-SPECIFIC EXPRESSION OF PROSAPOSIN MESSENGER-RNA IN MURINE TISSUES

Prosaposin is a multifunctional locus in humans and mice that encodes in tandem and in the same reading frame four glycoprotein activators, or saposins, of lysosomal hydrolases. These ubiquitously expressed gly coproteins and the precursor, prosaposin, have been proposed to functi on in glycosphingolipid catabolic pathways and glycolipid transport. T o characterize the temporal and spatial expression of the prosaposin l ocus, prenatal and postnatal mouse tissues were screened by in situ hy bridization with a mouse antisense riboprobe for prosaposin. Prenatall y, prosaposin mRNA was expressed differentially in the placenta and pr ominently in the decidua basalis and capsular's where expression was g estational age dependent. No other region of high-level expression was detectable in the prenatal mouse. In comparison, high-level different ial expression of prosaposin was clearly evident postnatally in a vari ety of organs, including secretory epithelial cells of the choroid ple xus, ependymal lining, upper trachea, esophagus, cortical tubules of t he kidney, sertoli cells of the testes and epididymis. Discrete locali zation of prosaposin mRNA expression was also found in neurons of the cerebral cortex, cerebellar cortex, and lateral columns of the spinal cord as well as in hepatocytes of the mature liver. Very high levels o f expression were found in specialized tissues including the Harderian glands and macrophages of lymph nodes, lungs, splenic tissue, and thy mus. These studies indicate that the expression of the prosaposin locu s, a presumed ''housekeeping'' gene, is under tissue- and cell-specifi c differential control. The spatial organization of expression suggest s a role for this locus in the expression of glycosphingolipid-storage diseases.