Copper phenotypes of Menkes disease fibroblasts. (A) Pedigrees of a family affected by Menkes disease. (B) ATP7A-null subject GM01981 was confirmed by immunoblot analysis. Asterisk denotes nonspecific band recognized by the antibody. Loading controls were performed with anti–β-actin antibodies (ACTB). (C) Wild-type (ATP7A+/y), carrier mother (ATP7A−/+, GM01983), and Menkes son (ATP7A−/y, GM01981) fibroblasts were imaged by two-photon microscopy with crisp-17. Color scale depicts copper-dependent emission ratio (0–2.5 range) at 570–640 nm/500–550 nm. (D) Copper was mobilized by the addition of the oxidizing reagent DTDP (100 µM). (Scale bar, 50 µm.) (E) Kymographs of cells in C (dashed line) with time 0 corresponding to the addition of DTDP. (F) Copper content phenotype confirmed by inductively coupled plasma mass spectrometry (one-way ANOVA followed by Dunnett's multiple comparisons; n = 3). (G) Fluorescence emission ratios before and after DTDP addition. Average ± SE from six independent experiments.