Prosaposin is a precursor of saposins A, B, C, and D. Saposins are indispensable for lysosomal hydrolysis of sphingolipids. The notion that prosaposin itself is likely involved in brain development led us to generate an anti-mouse prosaposin-specific antibody that do not cross-react with any of the processed saposins. We have used it to study expression of prosaposin in the brain of wild-type (WT) and saposin D knockout mice (Sap-D^-/-). Immunoblot studies indicated that prosaposin, already abundant in the brain of WT, was dramatically increased in Sap-D^-/-. By immunohistochemistry, the brain of WT was rich in prosaposin in hippocampal CA3 pyramidal neurons, tufted cells and mitral cells in olfactory bulb, and cerebellar Purkinje cells. In Sap-D^-/-, immunoreactivity of prosaposin was increased in these neurons, most notably in the CA3 pyramidal neurons which contained prosaposin immuno-positive inclusion bodies in the endoplasmic reticulum. Further characterization of these prosaposin-rich neurons may provide new insights into the physiological functions of prosaposin in the nervous system.

(Contributed by Kunihiko SUZUKI, M.J.A.)