Lentiviral vectors carrying enhancer elements of Hb9 promoter drive selective transgene expression in mouse spinal cord motor neurons

J Neurosci Methods. 2012 Mar 30;205(1):139-47. doi: 10.1016/j.jneumeth.2011.12.024. Epub 2012 Jan 8.

Abstract

Recombinant lentiviral vectors (rLVs) have emerged as versatile tools for gene delivery applications due to a number of favorable features, such as the possibility to maintain long-term transgene expression, the flexibility in the design of the expression cassettes and recent improvements in their biosafety profile. Since rLVs are able to infect multiple cell types including post-mitotic cells such as neurons and skeletal muscle cells, several studies have been exploring their application for the study and cure of neurodegenerative diseases. In particular, the introduction of rLVs carrying cell-type specific promoters could restrict the transgene expression either to neuronal or glial cells, thus helping to better dissect in vivo the role played by these cell populations in several neurodegenerative processes. In this study we developed rLVs carrying motor neuron specific regulatory sequences derived from the promoter of homeobox gene Hb9, and demonstrated that these constructs can represent a suitable platform for selective gene-targeting of murine spinal cord motor neurons, in vivo. This tool could be instrumental in the dissection of the molecular mechanisms involved in the selective degeneration of motor neurons occurring in Motor Neuron Diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',3'-Cyclic-Nucleotide Phosphodiesterases / metabolism
  • Animals
  • Anterior Horn Cells / metabolism
  • Astrocytes / metabolism
  • Astrocytes / physiology
  • Choline O-Acetyltransferase / metabolism
  • Coculture Techniques
  • Female
  • Fluorescent Dyes
  • Genetic Markers
  • Genetic Therapy / methods
  • Genetic Vectors
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins
  • Homeodomain Proteins / genetics*
  • Immunohistochemistry
  • Lentivirus / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Motor Neurons / physiology
  • Promoter Regions, Genetic / genetics*
  • Regulatory Sequences, Nucleic Acid / genetics
  • Transcription Factors / genetics*
  • Transfection
  • Transgenes / genetics*

Substances

  • Fluorescent Dyes
  • Genetic Markers
  • Glial Fibrillary Acidic Protein
  • Homeodomain Proteins
  • Transcription Factors
  • Hb9 protein, mouse
  • Green Fluorescent Proteins
  • Choline O-Acetyltransferase
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases