Characterization of transgenic mouse lines expressing Cre recombinase in the retina

Abstract

The mammalian retina consists of five major classes of neuronal cells, as well as glial cells, and it contains more than 50 cell types. The ability to manipulate gene expression in specific cell type(s) in the retina is important for understanding the molecular mechanisms of retinal function and diseases. The Cre/loxP recombination system has been shown to be a powerful tool, allowing gene deletion, over-expression, and ectopic expression in vivo in a cell- and tissue-specific fashion. The key to this tool is the availability of Cre mouse lines with cell- or tissue-type specific expression of Cre recombinase. To date, a large number of Cre-transgenic mouse lines have been generated to target Cre recombinase expression to specific neuronal and glial cell populations in the CNS; however, information about the expression patterns of Cre recombinase lines in the retina is largely lacking. In this study, we examined and characterized the expression patterns of Cre recombinase in the retinas of 15 Cre-transgenic mouse lines. Significant Cre-induced recombination or expression of Cre recombinase was observed in the majority of these lines. In particular, we found several Cre lines in which the Cre-induced recombination was found to target exclusively or predominantly a single type or class of retinal cells, including bistratified retinal ganglion cells, starburst amacrine cells, rod bipolar cells, and Müller glial cells. In other lines, the Cre-induced recombination was found in several retinal cell types. These Cre lines provide a valuable resource for retinal research.

Diverse Central Projection Patterns of Retinal Ganglion Cells

“…Our results are broadly consistent with those of a prior survey of GFP reporter lines (Siegert et al, 2009), and smaller scale screens of Cre driver lines (e.g. Ivanova et al, 2010). We then mapped and quantified all central projections of RGCs labeled in 26 of the lines, taking advantage of our Allen Mouse Brain Connectivity Atlas high-throughput imaging and data processing pipeline.…”

“…This morphology is characteristic of ON-DSGCs (Sun et al, 2006). Grik4-Cre also labels some CART-positive ooDSGCs as previously described (Ivanova et al, 2010), but in our hands predominant labeling was of the monostratified ON population.…”

“…Cluster 4 comprised two lines with arguably the highest specificity (Pcdh9-Cre_NP276 and Grik4-Cre) in which accessory optic nucleus projecting-ON-DSGCs were selectively labeled. Previous work in the Grik4-Cre line suggested that Cre+ cells were predominantly bistratified ooDSGCs (Ivanova et al, 2010), although we found that labeled cells are mostly, but not exclusively, of the monostratified type. The Pcdh9-Cre_NP276 line was even more specific to monostratifed RGCs than Grik4-Cre, and the central projection patterns reflect this increased specificity.…”

Visual Stimulation Switches the Polarity of Excitatory Input to Starburst Amacrine Cells

“…Retinas from C57BL/6 mice were used for calcium imaging. For targeted recordings of SACs we used two mouse lines; On- and Off-SACs were targeted with mGluR2-GFP mice (Watanabe et al, 1998) and On SACs were also targeted with Chatcre mouse (Ivanova et al, 2010) crossed with a reporter line (tdTomato, Jackson Labs). Connexin-36 knockout mice ( Cx36 KO ) were a generous gift from David Paul at Harvard Medical School (Deans et al, 2002).…”

Functional architecture of the retina: Development and disease

“…Nevertheless, the recent availability of genetic tools and transgenic lines with labeled cell types (Ivanova et al, 2010; Kim et al, 2010; Siegert et al, 2012) together with technical advancements in imaging techniques is facilitating a rapid acquisition of potential wiring diagrams of identified retinal cell types (Briggman et al, 2011; Helmstaedter et al, 2013). Here, we will provide an overview of the known synaptic organization and connectivity patterns of the adult retina, and discuss the knowledge that has accrued thus far concerning the mechanisms that underlie their construction and maintenance.…”