The giant panda(Ailuropoda melanoleuca)is an iconic bear native to China,famous for eating almost exclusively bamboo.This unusual dietary behavior for a carnivore is enabled by several key adaptations including low physical activity,reduced organ sizes and hypothyroidism leading to lowered energy expenditure.These adaptive phenotypes have been hypothesized to arise from a panda-unique single-nucleotide mutation in the dual-oxidase 2(DUOX2)gene,involved in thyroid hormone synthesis.To test this hypothesis,we created genome-edited mice carrying the same point mutation as the panda and investigated its effect on metabolic phenotype.Homozygous mice were 27％smaller than heterozygous and wild-type ones,had 13％lower body mass-adjusted food intake,55％decreased physical activity,lower mass of kidneys(11％)and brain(5％),lower serum thyroxine(T4:36％),decreased absolute(12％)and mass-adjusted(5％)daily energy expenditure,and altered gut microbiota.Supplementation with T4 reversed the effects of the mutation.This work uses a state-of-the-art genome editing approach to demonstrate the link between a single-nucleotide mutation in a key endocrine-related gene and profound adaptive changes in the metabolic phenotype,with great importance in ecology and evolution.