Extended Data Figure 3. Detailed schematic of multigeneration experiment.

Generation 1. Humanized mice were fed a high-MAC diet for four weeks then switched to a low-MAC diet. One week after diet switch, the mice were bred to generate a litter of pups. After three additional weeks on the low-MAC diet, generation two pups were born and remained in the cage with their mother for three weeks (generation 1 still consuming the low-MAC diet). After pups were weaned, generation 1 mice were returned to the high-MAC diet for six weeks. Generation 2. Pups were weaned from their mother at three weeks old onto a low-MAC diet, which they consumed for 10 weeks. Breeding pairs for generation 2 mice were set-up at 7 weeks old. After three additional weeks on the low-MAC diet, generation 3 pups were born and remained in the cage with their mother for three weeks (generation 2 still consuming the low-MAC diet). After pups were weaned, generation 2 mice were returned to the high-MAC diet for six weeks. Generations 3 and 4 followed the same protocol as generation 2 described above.