Extended Data Fig. 1: p110* construction and mouse model characterization.
From: Targeted therapy in patients with PIK3CA-related overgrowth syndrome
a, Left, Representation of p110 and iSH2 domain of the p85 subunit (striped bar). The iSH2 domain is important to stabilize the p110α protein. The p110* protein is a constitutively active chimaera that contains the iSH2 domain of p85 fused to the N terminus of p110 via a flexible glycine linker14 (right). b, To generate tissue-specific p110*-transgenic mice, a cloned loxP-flanked neoR-stop cassette was inserted into a modified version of pROSA26-1 followed by the cDNA encoding p110* and then a frt-flanked IRES–EGFP cassette and a bovine polyadenylation sequence (R26StopFLP110*)13. c, d, EGFP expression from flow cytometry experiments in the spleen of PIK3CAWT mice (n = 12) and PIK3CACAGG-CreER mice injected with either a single 40 mg kg−1 dose (c; n = 6 mice) or a single 4 mg kg−1 dose (d; n = 6 mice) of tamoxifen. Each curve is a different mouse. e, MRI examination of the PROS mouse model and efficacy of BYL719 treatment. Top, arrows show muscle hypertrophy in PIK3CACAGG-CreER mice before BYL719 treatment. This phenotype was reversed by BYL719 administration. Middle, arrows show scoliosis in PIK3CACAGG-CreER mice before BYL719 treatment, which was rescued by BYL719 administration. Bottom, arrows show arterial dilation in PIK3CACAGG-CreER mice before BYL719 treatment, which was reversed by BYL719 administration (n = 6 mice per group).
