Figure 4. 3M Syndrome is a ciliopathy.

(a) Schematic showing comparison of interactome to disease genes with the top scoring diseases shown (orange denotes known ciliopathies). The three 3M associated proteins are shown right, with the baits that retrieved them, and within the network (below). Matrix relationships are not shown in the table. (b) siRNA down-regulation of these genes in mpkCCD cells reveals that 3M genes are involved in ciliogenesis (knockdown of IFT88, known to affect ciliogenesis, is shown for comparison). (c) Fibroblasts from a 3M patient have fewer cilia than controls. The transition zone marker MKS1 is shown in red, acetylated tubulin in green and nuclear staining with DAPI in blue. Scale bars represent 5 μm. (d) Quantification of differences in ciliated cell count comparing 3M fibroblasts to those transformed with wild-type or mutant (p.H1464P) CUL7 or empty vector. Wild-type CUL7 restored ciliogenesis, while mutant CUL7 did not. (b–d) For all experiments biological triplicates with technical duplicates were performed. Error bars represent the s.e.m.