We hence report the generation and metabolic characterization of a new, CRISPR/Cas9-generated, global Mct8/Oatp1c1 dKO mouse, and confirm that these mice display a variety of key pathological hallmarks of AHDS, including increased mortality, central hypothyroidism, peripheral hyperthyroidism, severe motor impairment, decreased neuronal myelination, and enhanced T3 action in the liver, adipose tissue, and the bone. Here, SLC16A2 is linked to hyperthyroidism.