In contrast to CS patients that are heterozygous for HRAS mutation and display osteoporosis, in mice, bone loss occurred significantly only in CS KI/KI mice, while in +/KI mice these effects were mild at best because a single mutated allele may not have the strength to induce visible pathologies in mice (Figures 2, 3; Supplementary Figures S1, S2). Here, HRAS is linked to osteoporosis.