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Generation of IR D707A/ mice and mouse husbandry To generate IR D707A knock-in mice, a single-guide RNA (sgRNA) targeting the mouse Insr locus (5-GTTGTGCAGGTAATCCTCGAAGG-3), a single-stranded donor oligonucleotide containing the Insr p.D709A mutation (GATGCT) and a synonymous p.F707F mutation (TTCTTT), and Cas9 protein were co-injected into fertilized C57BL/6N zygotes

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