ArticleThe Biochemical journal2003
Analyses of temporal regulatory elements of the prosaposin gene in transgenic mice.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed, 10 citations in OpenAlex.
- Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice.BMC neuroscience · 2008Article
- Retinoid-related Orphan Receptors (RORs): Roles in Cellular Differentiation and Development.Advances in developmental biology (Amsterdam, Netherlands) · 2006Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The expression of prosaposin is temporally and spatially regulated at transcriptional and post-translational levels. Transgenic mice with various 5'-flanking deletions of the prosaposin promoter 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 activity 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 (ROR alpha)-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 cerebellum had low-level expression before birth and continued to increase into adulthood. In cerebrum, the endogenous mRNA showed similar expression profile to constructs 310LUC, 2400LUC and 234LUC, with the peak expression at 1 week and a decreased level in adult. In the brain of the newborn, 2400LUC was highly expressed in the trigeminal ganglion and brain stem regions when compared with the generalized expression pattern for endogenous prosaposin mRNA. These results suggest that the modifiers (ROR alpha- and Sp1-binding sites) residing within 310 bp of the 5'-flanking region mediate developmental regulation in the central nervous system and eye. Additional regulatory elements outside the 5' region of the 2400 bp promoter fragment appear to be essential for the physiological control of the prosaposin locus.
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