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Myotubularin is a lipid phosphatase implicated in endosomal trafficking in vitro, but with an unknown function in vivo. Mutations in myotubularin cause myotubular myopathy, a devastating congenital myopathy with unclear pathogenesis and no current therapies. Myotubular myopathy was the first described of a growing list of conditions caused by mutations in(More)
shocked (sho) is a zebrafish mutation that causes motor deficits attributable to CNS defects during the first2dof development. Mutant embryos display reduced spontaneous coiling of the trunk, diminished escape responses when touched, and an absence of swimming. A missense mutation in the slc6a9 gene that encodes a glycine transporter (GlyT1) was identified(More)
The process by which light touch in vertebrates is transformed into an electrical response in cutaneous mechanosensitive neurons is a largely unresolved question. To address this question we undertook a forward genetic screen in zebrafish (Danio rerio) to identify mutants exhibiting abnormal touch-evoked behaviors, despite the presence of sensory neurons(More)
Myotubularins are a family of dual-specificity phosphatases that act to modify phosphoinositides and regulate membrane traffic. Mutations in several myotubularins are associated with human disease. Sequence changes in MTM1 and MTMR14 (also known as Jumpy) have been detected in patients with a severe skeletal myopathy called centronuclear myopathy. MTM1 has(More)
Mutations in the gene encoding TRPM7 (trpm7), a member of the Transient Receptor Potential (TRP) superfamily of cation channels that possesses an enzymatically active kinase at its C terminus, cause the touch-unresponsive zebrafish mutant touchdown. We identified and characterized a new allele of touchdown, as well as two previously reported alleles, and(More)
A screen for zebrafish motor mutants identified two noncomplementing alleles of a recessive mutation that were named non-active (nav(mi89) and nav(mi130)). nav embryos displayed diminished spontaneous and touch-evoked escape behaviors during the first 3 days of development. Genetic mapping identified the gene encoding Na(V)1.6a (scn8aa) as a potential(More)
24 25 The molecular and physiological basis of the touch-unresponsive zebrafish mutant fakir has 26 remained elusive. Here we report that the fakir phenotype is caused by a missense mutation in the gene 27 encoding voltage-gated calcium channel 2.1b (CACNA1Ab). Injection of RNA encoding wild type 28 CaV2.1 restores touch responsiveness in fakir mutants,(More)
Several zebrafish P2X receptors (zP2X1, zP2X2, and zP2X5.1) have been reported to produce little or no current although their mammalian orthologs produce functional homomeric receptors. We isolated new cDNA clones for these P2X receptors that revealed sequence variations in each. The new variants of zP2X1 and zP2X5.1 produced substantial currents when(More)
Following their synthesis in the endoplasmic reticulum (ER), voltage-gated sodium channels (NaV) are transported to the membranes of excitable cells, where they often cluster, such as at the axon initial segment of neurons. Although the mechanisms by which NaV channels form and maintain clusters have been extensively examined, the processes that govern(More)
In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for(More)