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A translational profiling approach for the molecular characterization of CNS cell types.

The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations. Using bacterial artificial chromosome (BAC) transgenic mice that express EGFP-tagged ribosomal protein L10a in defined cell populations, we have developed a methodology for affinity purification of polysomal mRNAs from genetically defined cell populations in the brain. The utility of this approach is illustrated by the comparative analysis of four types of neurons, revealing hundreds of genes that distinguish these four cell populations. We find that even two morphologically indistinguishable, intermixed subclasses of medium spiny neurons display vastly different translational profiles and present examples of the physiological significance of such differences. This genetically targeted translating ribosome affinity purification (TRAP) methodology is a generalizable method useful for the identification of molecular changes in any genetically defined cell type in response to genetic alterations, disease, or pharmacological perturbations.

Pubmed ID: 19013281

Authors

  • Heiman M
  • Schaefer A
  • Gong S
  • Peterson JD
  • Day M
  • Ramsey KE
  • Suárez-Fariñas M
  • Schwarz C
  • Stephan DA
  • Surmeier DJ
  • Greengard P
  • Heintz N

Journal

Cell

Publication Data

November 14, 2008

Associated Grants

  • Agency: NIDA NIH HHS, Id: 5F32DA021487
  • Agency: NCRR NIH HHS, Id: 5UL1RR024143
  • Agency: NIA NIH HHS, Id: AG09464
  • Agency: NIDA NIH HHS, Id: DA10044
  • Agency: NIDA NIH HHS, Id: F32 DA021487
  • Agency: NIDA NIH HHS, Id: F32 DA021487-01
  • Agency: NIDA NIH HHS, Id: F32 DA021487-02
  • Agency: NIMH NIH HHS, Id: MH074866
  • Agency: NINDS NIH HHS, Id: NS34696
  • Agency: NIA NIH HHS, Id: P01 AG009464
  • Agency: NIA NIH HHS, Id: P01 AG009464-16A1
  • Agency: NIA NIH HHS, Id: P01 AG009464-17
  • Agency: NIDA NIH HHS, Id: P01 DA010044
  • Agency: NIDA NIH HHS, Id: P01 DA010044-09
  • Agency: NIDA NIH HHS, Id: P01 DA010044-10
  • Agency: NIDA NIH HHS, Id: P01 DA010044-11
  • Agency: NIMH NIH HHS, Id: P50 MH074866
  • Agency: NIMH NIH HHS, Id: P50 MH074866-01
  • Agency: NIMH NIH HHS, Id: P50 MH074866-010001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-010002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-010005
  • Agency: NIMH NIH HHS, Id: P50 MH074866-017204
  • Agency: NIMH NIH HHS, Id: P50 MH074866-019001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-019002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-02
  • Agency: NIMH NIH HHS, Id: P50 MH074866-020001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-020002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-020005
  • Agency: NIMH NIH HHS, Id: P50 MH074866-029001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-029002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-03
  • Agency: NIMH NIH HHS, Id: P50 MH074866-030001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-030002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-030005
  • Agency: NIMH NIH HHS, Id: P50 MH074866-039001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-039002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-04
  • Agency: NIMH NIH HHS, Id: P50 MH074866-040001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-040002
  • Agency: NIMH NIH HHS, Id: P50 MH074866-040005
  • Agency: NIMH NIH HHS, Id: P50 MH074866-049001
  • Agency: NIMH NIH HHS, Id: P50 MH074866-049002
  • Agency: NINDS NIH HHS, Id: R37 NS034696
  • Agency: NINDS NIH HHS, Id: R37 NS034696-11
  • Agency: NINDS NIH HHS, Id: R37 NS034696-12
  • Agency: NINDS NIH HHS, Id: R37 NS034696-13
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Brain
  • Central Nervous System
  • Chromosomes, Artificial, Bacterial
  • Cocaine
  • Dopamine Uptake Inhibitors
  • Genetic Techniques
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Neurons
  • Protein Biosynthesis
  • Ribosomes