Analyses of temporal regulatory elements of the prosaposin gene in transgenic mice

The expression of prosaposin is temporally and spatially regu-lated at transcriptional and post-translational levels. Transgenic mice with various 5«-flanking deletions of the prosaposin pro-moter fused to luciferase (LUC) reporters were used to define its temporal regulatory region. LUC expression in the transgenic mice carrying constructs with 234 bp (234LUC), 310 bp (310LUC) or 2400 bp (2400LUC) of the 5«-flanking region was analysed in the central nervous system and eye throughout development. For 310LUC and 2400LUC, low-level LUC ac-tivity was maintained until embryonal day 18 in brain, eye and spinal cord. The peak level of LUC activity was at birth, with return to a plateau (1}3 of peak) throughout adulthood. Deletion of the region that included the retinoic acid-receptor-related orphan receptor (RORa)-binding site and sequence-specific transcription factor (Sp1) cluster sites (44–310 bp) suppressed the peak of activity. By comparison, the peak level for 234LUC was shifted 2 weeks into neonatal life in the brain, but not in the eye, and no peak of activity was observed in the spinal cord. The endogenous prosaposin mRNA in eye, spinal cord and cere