γ1(R70Q) and γ1(−/−) line generation

CRISPR/Cas9 genome editing was performed according to previous work⁶⁰. All the single guide RNAs (sgRNAs) were designed based on the CHOP-CHOP web-based tool (https://chopchop.cbu.uib.no). The same sgRNA was used to generate both γ_1(R70Q) and γ1(−/−) mutant lines. The single-strand DNA (ssDNA) to generate γ_1(R70Q) was designed to contain 45 bp of homology arm and two base-pair mutations in the region encompassing the coding sequence for γ1 amino acid residue R70. Alt-R S.p. HiFi Cas9 Nuclease, Alt-R sgRNA and the ssDNA template were purchased from IDT (Supplementary Table 2 provides sequences). One-cell-stage embryos were injected with 1–2 nl of a solution containing Cas9 enzyme (200 ng µl⁻¹), sgRNA (20 ng µl⁻¹), ssDNA (40 ng µl⁻¹), KCl (0.2 M) and 1% phenol red. The F0 generation was genotyped by fin-clipping to identify potential founders (Extended Data Fig. 7e,f; Supplementary Table 2 contains primers sequences). Selected founders were then backcrossed with the GRZ-AD strain for four generations to reduce the potential presence of background mutations induced by CRISPR editing.