Uncovering genes required for neuronal morphology by morphology-based gene trap screening with a revertible retrovirus vector

FASEB J. 2012 Nov;26(11):4662-74. doi: 10.1096/fj.12-207530. Epub 2012 Aug 8.

Abstract

The molecular mechanisms of neuronal morphology and synaptic vesicle transport have been largely elusive, and only a few of the molecules involved in these processes have been identified. Here, we developed a novel morphology-based gene trap method, which is theoretically applicable to all cell lines, to easily and rapidly identify the responsible genes. Using this method, we selected several gene-trapped clones of rat pheochromocytoma PC12 cells, which displayed abnormal morphology and distribution of synaptic vesicle-like microvesicles (SLMVs). We identified several genes responsible for the phenotypes and analyzed three genes in more detail. The first gene was BTB/POZ domain-containing protein 9 (Btbd9), which is associated with restless legs syndrome. The second gene was cytokine receptor-like factor 3 (Crlf3), whose involvement in the nervous system remains unknown. The third gene was single-stranded DNA-binding protein 3 (Ssbp3), a gene known to regulate head morphogenesis. These results suggest that Btbd9, Crlf3, and Ssbp3 regulate neuronal morphology and the biogenesis/transport of synaptic vesicles. Because our novel morphology-based gene trap method is generally applicable, this method is promising for uncovering novel genes involved in the function of interest in any cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins
  • Blotting, Southern
  • Cloning, Molecular
  • Gene Expression Regulation / physiology*
  • Gene Knockdown Techniques
  • Genetic Vectors
  • Karyotype
  • Mutagenesis, Insertional / methods*
  • Neurons / cytology*
  • Neurons / metabolism*
  • PC12 Cells
  • Pore Forming Cytotoxic Proteins
  • RNA, Small Interfering
  • Rats
  • Retroviridae
  • Transcription Factors

Substances

  • Bacterial Toxins
  • Pore Forming Cytotoxic Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • aerolysin