The resistant Cyp1b1-ko mice were also bred with WT mice and their heterozygote progeny were crossed with Cyp1b1-ko mice (Figure 3D). These progeny clearly segregated into two groups: offspring resembling the suppressed phenotype of the original Cyp1b1-ko mice and mice with the resistant phenotype (Figures 3F and S3B). Extended back-crossing through 5 generations has restored the phenotype observed in the mice represented in Figure 1 (not shown). Gene changes are, therefore, introduced from inter-breeding of Cyp1b1-ko mice that promote obesity. The suppression mechanisms in Cyp1b1-ko mice are restored when replaced by their WT counterparts.
