Fig. 3

Genetic strategy to label homoallelic and heteroallelic synaptic interactions using dual-eGRASP. A Upon crossing wild-type male mice carrying an X-linked Cre (such as Hprt^Cre in blue text) to heterozygous female mice carrying a mutation in an X-linked gene of interest (such as Cdkl5^KO in pink text, as an example), Cre-expressing cells in the F1 female progenies will always express wild-type Cdkl5⁺, while Cdkl5^KO-expressing cells will be Cre negative, due to the linkage of Hprt^Cre and Cdkl5⁺ on the same X-chromosome (WT with Cre, mutant without Cre). B When the dual-eGRASP system is delivered using Cre-ON and Cre-OFF AAV, specific synaptic interactions can be labeled in these F1 offspring. In this example, presynaptic cell populations are labeled using Cre-ON yellow pre-eGRASP and Cre-OFF cyan pre-eGRASP, while postsynaptic cells are labeled using Cre-ON membrane-bound red reporter with post-eGRASP and Cre-OFF membrane-bound far-red reporter with post-eGRASP