Models of Distal Arthrogryposis and Lethal Congenital Contracture Syndrome

Figures

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  Figure 1. The curved spinal phenotype associated with both smyhc1+/R673H and smyhc1R673H/R673H genotypes is normalized with the myosin inhibitor para-aminoblebbistatin. Embryos were treated from 24–48 hpf and photographed at 48 hpf. Treated embryos are shown below DMSO treated controls. Unlike the newer myosin inhibitors that are being developed, para-aminoblebbistatin has many toxic effects, including lethal cardiac edema, which limits its use as a human therapeutic. These images are similar to those published in [16].

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  Figure 2. DA associated TPM2 variants cause muscle phenotypes in Drosophila. Confocal micrographs of live L3 larva that express GFP-tagged TPM2 variants in skeletal muscles (body wall muscles). Mef2.Gal4 was used to activate UAS.TPM2 transgenes. Lateral and dorsal views are shown for each genotype. (A,B) Larva that express TPM2.GFP showed normal muscle histology. Larva that expresses TPM2.E41K.GFP (C,D) or TPM2.R91G.GFP (E,F). GFP have rounded myofibers that appear to result from internal tears (arrows; note affected muscles remain associated with tendons at segment boundaries) and shortened segments that could be due to hypercontractile muscles (arrowheads). Thoracic segments (T1–T3) and abdominal segments (A1–A8) are labeled. Scale bars, 500 mM. Previously unpublished data.