A transgenic mouse line expressing cre recombinase in undifferentiated postmitotic mouse retinal bipolar cell precursors

PLoS One. 2011;6(10):e27145. doi: 10.1371/journal.pone.0027145. Epub 2011 Oct 31.

Abstract

Approaches for manipulating cell type-specific gene expression during development depend on the identification of novel genetic tools. Here, we report the generation of a transgenic mouse line that utilizes Vsx2 upstream sequences to direct Cre recombinase to developing retinal bipolar cells. In contrast to the endogenous Vsx2 expression pattern, transgene expression was not detected in proliferating retinal progenitor cells and was restricted to post-mitotic bipolar cells. Cre immunolabeling was detected in rod bipolar cells and a subset of ON and OFF cone bipolar cells. Expression was first observed at postnatal day 3 and was detectable between 24 hours and 36 hours after the last S-phase of the cell cycle. The appearance of Cre-immunolabeled cells preceded the expression of bipolar cell type-specific markers such as PKCα and Cabp5 suggesting that transgene expression is initiated prior to terminal differentiation. In the presence of a constitutive conditional reporter transgene, reporter fluorescence was detected in Cre-expressing bipolar cells in the mature retina as expected, but was also observed in Cre-negative Type 2 bipolar cells and occasionally in Cre-negative photoreceptor cells. Together these findings reveal a new transgenic tool for directing gene expression to post-mitotic retinal precursors that are mostly committed to a bipolar cell fate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Female
  • Homeodomain Proteins / physiology*
  • Humans
  • Integrases
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitosis / physiology*
  • Neurons / cytology
  • Neurons / metabolism
  • Retina / cytology
  • Retina / metabolism*
  • Retinal Bipolar Cells / cytology
  • Retinal Bipolar Cells / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / physiology*
  • Transgenes / physiology*

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • Vsx2 protein, mouse
  • Cre recombinase
  • Integrases