Crispr cas9 mediated genome editing technology

The Ido1 and Qprt knockout mice were generated using CRISPR/Cas9‐mediated genome editing technology from Cyagen. Genomic DNA was extracted from the mouse tails using a DNA extraction kit (Qiagen) and subjected to Sanger DNA sequencing to confirm the homozygous knockout status. For the supplementation treatment, four‐week‐old Ido1^−/− and Qprt^−/− mice were fed with nicotinamide riboside (NR, Shanghai Biochempartner Co., Ltd) at a dose of 400 mg/kg/day for 7 months. Wild‐type C57/BL6 mice were purchased from Beijing Vital River Experimental Animals Centre. The mice were housed under a 12‐h light–dark cycle and maintained at a room temperature of 20–25°C with access to food and water ad libitum.

The YTHDF1 knockout (YTHDF1^-/-) mice were generated by CRISPR-cas9-mediated genome editing technology (Cyagen Biosciences). MFG-E8 knockout (MFG-E8^-/-) mice were generated by knocking out 2-6 exons of MFG-E8 gene using CRISPR/Cas9 gene editing technology (Shanghai Model Organisms, Supplementary Figure 11). The primer sequences used were presented in supplementary table 1. Animal studies were carried out in a specific pathogen-free (SPF) animal facility, and littermates were also cohoused during experiments to reduce variation in the microbiome and environment. All animal care and experimental procedures were approved by the Ethics Committee of Xi'an Jiaotong University, according to the National Health Guidelines for the Care and Use of Laboratory Animals.

Wild-type C57BL/6 mice were purchased from the Experimental Animal Center of Anhui Province (Hefei, China). Lamtor2^fl/+ mice (C57BL/6J) were generated by CRISPR-Cas9-mediated genome-editing technology (Cyagen Biosciences, China) targeting exons 1 to 3. Lamtor2 conditional knockout mice were generated by crossing Lamtor2^fl/fl mice with Lyz2-Cr_e^+/− transgenic mice. Meanwhile, we obtained Lamtor2^fl/fl littermate controls. All experiments involving mice were approved by the Institutional Animal Care and Use Committee of Anhui Medical University (Hefei, China).