A proportion of Cyp1b1-ko mice are resistant to obesity suppression on the HFD, while retaining other features of the Cyp1b1-ko-phenotype, notably in the endothelia and pericytes [18–19]. From these more obese mice, we generated a colony in which 80 percent of the mice exhibited WT levels of DIO and elevated blood glucose levels (resistant Cyp1b1-ko mice) (Figure 3D). Selection for low obesity by mating male and female mice that remained lean when challenged with the HFD (S1&2 mice) failed to improve the proportion of lean Cyp1b1-ko progeny (Figures 3E and S3A). Both suppressed and super-obese pups (BW 20–30 percent above normal) were obtained within the same S1&2 litters. Breeding of the most obese Cyp1b1-ko male and female mice (L1&2 mice) generated progeny that were predominantly super-obese. Similar incomplete penetrance of Cyp1b1 deletion effects have also been observed in humans and mice with respect to congenital glaucoma, which is associated with loss of function CYP1B1 mutations.
