A Chrnb3-Cre BAC transgenic mouse line for manipulation of gene expression in retinal ganglion cells

Genesis. 2019 Sep;57(9):e23305. doi: 10.1002/dvg.23305. Epub 2019 May 14.

Abstract

The mechanisms by which retinal ganglion cells (RGCs) make specific connections during development is an intense area of research and have served as a model for understanding the general principles of circuit wiring. As such, genetic tools allowing for specific recombination in RGCs are critical to further our understanding of the cell-specific roles of different genes during these processes. However, many RGC-specific Cre lines have drawbacks, due to their broad expression in other cell types and/or retinorecipient regions or lack of expression in broad swaths of the retina. Here, we characterize a Cre BAC transgenic line driven by elements of the cholinergic receptor nicotinic beta 3 subunit (Chrnb3). We show that Cre expression is restricted to RGCs in the retina and sparsely expressed in the brain, importantly excluding retinorecipient regions. Furthermore, Chrnb3-Cre mice label a wide variety of RGCs distributed throughout the retina and Cre activity is detected embryonically, shortly following RGC differentiation. Finally, we find that Chrnb3-Cre-labeled RGCs innervate multiple retinorecipient areas that serve both image-forming and nonimage forming functions. Thus, this genetic tool will be of broad use to investigators studying the RGC-specific contributions of genes to visual circuit development.

Keywords: Chrnb3; Cre; retinal ganglion cell; retinal targeting.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromosomes, Artificial, Bacterial*
  • Gene Expression Regulation*
  • Gene Transfer Techniques
  • Integrases / genetics
  • Mice, Transgenic / genetics*
  • Receptors, Nicotinic / genetics*
  • Retinal Ganglion Cells / metabolism*

Substances

  • Receptors, Nicotinic
  • nicotinic receptor beta3, mouse
  • Cre recombinase
  • Integrases