Construction and Analysis of an Allelic Series of Ccn1 Knockin Mice

Abstract

The embryonic lethality of mice with conventional global knockout of Ccn1 (Cyr61) precludes analysis of Ccn1 functions in late embryonic development or in adulthood. To circumvent this limitation, we have generated conditional knockout mice that allow cell type-specific deletion of Ccn1, and constructed an allelic series of Ccn1 knockin mice that express CCN1 defective for binding specific integrins in lieu of the wild type protein. Here we describe the construction of these mice and discuss how analysis of these animals can provide unique insights into Ccn1 functions mediated through specific integrin receptors. It is anticipated that future analysis of mice carrying specific mutations in genes of the Ccn family will be greatly facilitated by application of the CRISPR/Cas9 gene editing methodology.

Astrocyte CCN1 stabilizes neural circuits in the adult brain

“…1H) validating the transcriptomics, male mice were used. For adult knock-out experiments, CCN1 fl/fl mice were a gift from Dr. Lester Lau ( 36 ) and were maintained on a C57Bl6/J background. These mice were crossed to mice expressing tamoxifen inducible Cre recombinase under an astrocytic promoter for temporal elimination (Aldh1l1cre-Ert2, Jax 029655( 78 )).…”

“…Conversely, we hypothesized that removing CCN1 from astrocytes in adulthood would result in increased plasticity. To knock out CCN1 specifically in astrocytes, we crossed a Ccn1 floxed mouse ( 36 ) with a tamoxifen-inducible Aldh1l1-CreERT2 mouse ( 37 ), with tamoxifen given after 1 month of age (Fig. 2G).…”