Journal
JOURNAL OF NEUROGENETICS
Volume 31, Issue 4, Pages 325-336Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/01677063.2017.1393076
Keywords
qvr/sss; Shaker; sleepless; RNA editing; Ly-6/ neurotoxin superfamily; synaptic plasticity; potassium current inactivation; ether-induced leg shaking
Categories
Funding
- NIH (USA) [NS26528, GM80255, AG047612, AG051513]
- Natural Sciences and Engineering Research Council Discovery Grant (Canada)
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Our earlier genetic screen uncovered a paraquat-sensitive leg-shaking mutant quiver(1) (qvr(1)), whose gene product interacts with the Shaker (Sh) Kthorn channel. We also mapped the qvr locus to EY04063 and noticed altered day-night activity patterns in these mutants. Such circadian behavioral defects were independently reported by another group, who employed the qvr(1) allele we supplied them, and attributed the extreme restless phenotype of EY04063 to the qvr gene. However, their report adopted a new noncanonical gene name sleepless (sss) for qvr. In addition to qvr(1) and qvrEY, our continuous effort since the early 2000s generated a number of novel recessive qvr alleles, including ethyl methanesulfonate (EMS)-induced mutations qvr(2) and qvr(3), and P-element excision lines qvr(ip6) (imprecise jumpout), qvr(rv7), and qvrrv(9) (revertants) derived from qvrEY. Distinct from the original intron-located qvr(1) allele that generates abnormal-sized mRNAs, qvr(2), and qvr(3) had their lesion sites in exons 6 and 7, respectively, producing nearly normal-sized mRNA products. A set of RNA-editing sites are nearby the lesion sites of qvr(3) and qvrEY on exon 7. Except for the revertants, all qvr alleles display a clear ether-induced leg-shaking phenotype just like Sh, and weakened climbing abilities to varying degrees. Unlike Sh, all shaking qvr alleles (except for qvr(f01257)) displayed a unique activity-dependent enhancement in excitatory junction potentials (EJPs) at larval neuromuscular junctions (NMJs) at very low stimulus frequencies, with qvrEY displaying the largest EJP and more significant NMJ overgrowth than other alleles. Our detailed characterization of a collection of qvr alleles helps to establish links between novel molecular lesions and different behavioral and physiological consequences, revealing how modifications of the qvr gene lead to a wide spectrum of phenotypes, including neuromuscular hyperexcitability, defective motor ability and activity-rest cycles.
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