Generation of Astrocyte-Selective Cre Driver Lines With Distinct Onsets of Recombination Activity During Development

Abstract

Astrocytes are a major glial cell type, playing multiple roles in the development, function, and pathogenesis of the brain. Accordingly, neuronal–astrocyte communication is an important research area. However, because these cell types share the same developmental origin, selective manipulation of each cell type is needed for precise mechanistic understanding. Here, we generated two new Cre driver lines for selective gene manipulation in astrocytes: Slc7a10-IRES-Cre and Aldh1l1-IRES-Cre. An internal ribosome entry site (IRES)-Cre cassette was knocked-in to the 3′-untranslated region of the solute carrier family 7 member 10 (Slc7a10) or aldehyde dehydrogenase 1 family member L1 (Aldh1l1) locus without disrupting gene function. The Slc7a10-IRES-Cre line underwent highly selective recombination in astrocytes of the brain, apart from choroid plexus epithelial cells. The onset of recombination began after completion of differentiation in the astrocyte lineage. By contrast, the Aldh1l1-IRES-Cre line began recombination during astrocyte differentiation at early postnatal stages. Some leaky expression was observed in the oligodendrocyte lineage, probably due to early onset of Cre expression in an uncommitted glial progenitor state. Together, the combination of the two deleter lines with distinct temporal Cre expression patterns serves as valuable tools to understand the development and function of astrocytes.