Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments

Sylvie Vandaele, Daniel T. Nordquist, Rodney M. Feddersen, Irene Tretjakoff, Alan C. Peterson, Harry T. Orr

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

The Purkinje cell protein 2 [Pcp-2] is expressed in cerebellar Purkinje cells and retinal bipolar neurons. To illuminate how Pcp-2 expression is restricted to only two neuronal types and to derive tools to express heterologous genes in these neuronal subpopulations, genomic sequences of the mouse Pcp-2 gene have been cloned and flanking sequences have been evaluated as a source of neuron-specific regulatory elements. An upstream region with homology to other genes expressed in neurons was identified and a hybrid gene containing this sequence was constructed by ligating 0.4 kb of upstream and 0.3 kb of downstream Pcp-2-flanking DNA to lacZ. Transgenic mice bearing this construct exhibited β-galactosidase in a wide array of neuron types, suggesting that this sequence may play an important role in specifying neuronal expression. Addition of a further 3.1 kb of Pcp-2 upstream sequences restricted expression of β-galactosidase to a small number of neuron types and most notably to Purkinje cells within parasagitally oriented cerebellar compartments. The presence of elements lying within the 3.1-kb upstream region and acting to specifically restrict Pcp-2 expression is therefore suggested. Moreover, as β-galactosidase was not expressed in the bipolar cells of these transgenic mice, retinal expression of the endogenous Pcp-2 gene must involve elements in addition to those conferring expression within Purkinje cells.

Original languageEnglish (US)
Pages (from-to)1136-1148
Number of pages13
JournalGenes and Development
Volume5
Issue number7
DOIs
StatePublished - Jul 1991

Keywords

  • Cerebellar compartments
  • Neuron-specific
  • Pcp-2
  • Purkinje
  • Transgene

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