Rodents were purchased or maintained under pathogen-free conditions. All animal experiments were done according to protocols approved by the Animal Studies Committee of Washington University School of Medicine and in accordance with the National Institute of Health guidelines. UBC13loxP/loxP and GABAα6-Cre have been described49 (link), 68 (link).
To generate RNF8loxP/loxP mice, a loxP/FRT Neo cassette was placed flanking exons 6 and 7 of the RNF8 gene, as shown in Supplementary Fig.2a . The targeting construct was transfected by electroporation into BA1 (C57BL/6 × 129/SvEv) hybrid embryonic stem (ES) cells. Targeted BA1 hybrid ES cells were microinjected into C57BL/6 blastocysts. Resulting chimeras with a high percentage agouti coat color were mated to C57BL/6 FLP mice to remove the Neo cassette. The gene targeting and generation of RNF8loxP/loxP mice were performed by Ingenious Targeting Laboratory. The RNF8loxP/loxP mice were backcrossed onto C57BL/6 background. For the RNF8 conditional knockout granule neuron-specific mice (within the cerebellar cortex), RNF8loxP/loxP mice were mated with transgenic mice expressing Cre recombinase under the promoter of the Math1 gene (B6.Cg-Tg(Atoh1-cre)1Bfri/J, Jackson Laboratory)41 (link). Genotyping for the RNF8 flox allele was performed with the following PCR primers: 5′-GGTTACCACTCCATAACCATCTGTACG-3′; 5′-CAGAAGGTAGCAACAGAACACGACG-3′.
To generate RNF8loxP/loxP mice, a loxP/FRT Neo cassette was placed flanking exons 6 and 7 of the RNF8 gene, as shown in Supplementary Fig.