PMID- 11085950 OWN - NLM STAT- MEDLINE DCOM- 20010118 LR - 20181113 IS - 0264-6021 (Print) IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 352 Pt 2 IP - Pt 2 DP - 2000 Dec 1 TI - Prosaposin: promoter analysis and central-nervous-system-preferential elements for expression in vivo. PG - 549-56 AB - The expression of prosaposin is temporally and spatially regulated at the transcriptional and post-translational levels. In vitro, the mouse prosaposin promoter contains functional RORE [retinoic acid-receptor-related orphan receptor alpha subunit (RORalpha)-binding element], Sp1 and U (unknown) sites within 310 bp directly 5' to the transcription start site and additional elements within 2400 bp 5' to the transcription start site. To elucidate promoter regions important to tissue-preferential expression in vivo, transgenic mice were created with 5'-flanking deletions of the prosaposin gene fused to a luciferase reporter. Nearly exclusive expression was observed in cerebrum, cerebellum and eyes of adult transgenic mice containing constructs with 234-310 bp of 5'-flanking DNA. This central nervous system (CNS) expression was due to the presence of RORE and overlapping Sp1 sites in this region. Internal deletion of RORE and the Sp1 cluster from the longer constructs with 2400 bp of 5'-flanking DNA significantly diminished expression in the CNS. The appearance of substantial visceral tissue (e.g. liver, spleen, lung, kidney, thymus and heart) expression was obtained with transgenic mice bearing constructs with 742-2400 bp of 5'-flanking DNA. The cellular localization of luciferase reporter-gene expression from these constructs corresponded closely with that for prosaposin. These results define important CNS and visceral regulatory regions in the promoter in vivo and may be sufficient to account for the majority of prosaposin's tissue-preferential expression. FAU - Sun, Y AU - Sun Y AD - Division and Program in Human Genetics, Children's Hospital Medical Center, 3333 Burnet Avenue, TCHRF 1042, Cincinnati, OH 45229-3039, USA. FAU - Jin, P AU - Jin P FAU - Witte, D P AU - Witte DP FAU - Grabowski, G A AU - Grabowski GA LA - eng GR - NS 34071/NS/NINDS NIH HHS/United States GR - NS 36681/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (Glycoproteins) RN - 0 (Psap protein, mouse) RN - 0 (Saposins) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Central Nervous System/*metabolism MH - *Gene Expression MH - Glycoproteins/*genetics MH - Luciferases/genetics MH - Mice MH - Mice, Transgenic MH - *Promoter Regions, Genetic MH - Saposins MH - Transgenes PMC - PMC1221488 EDAT- 2000/11/22 11:00 MHDA- 2001/02/28 10:01 PMCR- 2001/06/01 CRDT- 2000/11/22 11:00 PHST- 2000/11/22 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/11/22 11:00 [entrez] PHST- 2001/06/01 00:00 [pmc-release] PST - ppublish SO - Biochem J. 2000 Dec 1;352 Pt 2(Pt 2):549-56.