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Intragenic sequences are required for cell type-specific and injury-induced expression of the rat peripherin gene
T Belecky-Adams1, D C Wight, J J Kopchick
1Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Ohio 45267-0521.
Insights
Researchers identified specific peripherin gene sequences essential for its expression in nerve cells and its upregulation after injury. This finding aids understanding of nerve regeneration and development.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Peripherin is a type III intermediate-filament protein crucial for axon development and regeneration.
- Its precise role and regulatory mechanisms in specific neuronal cell types remain incompletely understood.
Purpose of the Study:
- To identify the specific sequences within the peripherin gene responsible for its cell type-specific expression.
- To determine the genetic elements controlling the increase in peripherin expression following axonal injury.
Main Methods:
- Utilized transgenic mouse models to study peripherin gene regulation.
- Linked 5.8 kilobases of the peripherin 5' flanking sequence to a reporter gene.
- Investigated the impact of intragenic sequences on gene expression.
Main Results:
- Temporal and nervous system-specific expression was achieved with 5.8 kb of 5' flanking sequence.
- Precise cell type-specific expression, including in dorsal root ganglion and spinal cord motor neurons, required intragenic sequences.
- Peripherin transgenes were upregulated in these neurons following nerve injury.
Conclusions:
- Identified key peripherin gene regulatory elements, including intragenic sequences, essential for cell-specific expression and injury-induced upregulation.
- Provides insights into the molecular mechanisms governing peripherin expression in neuronal development and repair.
Abstract:
Peripherin is a 57 kDa type III intermediate-filament protein that is thought to play a role in axonogenesis both during development and following nerve injury (Oblinger et al., 1989; Escurat et al., 1990; Gorham et al., 1990; Troy et al., 1990b). We have used transgenic mouse technology to define peripherin gene sequences that are necessary for cell type-specific expression and for the increase in peripherin that occurs in response to axonal injury. Correct temporal and nervous system-specific expression resulted when 5.8 kilobases of peripherin 5' flanking sequence were linked to a reporter gene, but precise cell type-specific expression was achieved only when intragenic sequences were included. When intragenic sequences were present, peripherin transgenes were expressed in dorsal root ganglion neurons and spinal cord motor neurons and were upregulated in these cells following nerve injury.