DMCA
An MYH9 Human Disease Model in Flies: site-directed mutagenesis of the Drosophila nonmuscle myosin II results in hypomorphic alleles with dominant character (2007)
BibTeX
@MISC{Franke07anmyh9,
author = {Josef D. Franke and Ruth A. Montague and Wayne L. Rickoll and Daniel P. Kiehart and Daniel P. Kiehart},
title = {An MYH9 Human Disease Model in Flies: site-directed mutagenesis of the Drosophila nonmuscle myosin II results in hypomorphic alleles with dominant character},
year = {2007}
}
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Abstract
We investigated whether or not human disease-causing, amino acid substitutions in MYH9 could cause dominant phenotypes when introduced into the sole nonmuscle myosin II heavy chain in Drosophila melanogaster (zip/MyoII). We characterized in vivo the effects of four MYH9-like mutations in the myosin rod – R1171C, D1430N, D1847K and R1939X – which occur at highly conserved residues. These engineered mutant heavy chains resulted in D. melanogaster nonmuscle myosin II with partial wild-type function. In a wild-type genetic background, mutant heavy chains were overtly recessive and hypomorphic: each was able to substitute partially for endogenous nonmuscle myosin II heavy chain in animals lacking zygotically produced heavy chain (but the penetrance of rescue was below Mendelian expectation). Moreover, each of the four mutant heavy chains exhibits dominant characteristics when expressed in a sensitized genetic background (flies heterozygous for RhoA mutations). Thus these zip/MyoII MYH9 alleles function, like certain other hypomorphic alleles, as excellent bait in screens for genetic interactors. Our conjecture is that these mutations in D. melanogaster behave comparably to their parent mutations in humans. We further characterized these
Keyphrases
hypomorphic allele drosophila nonmuscle myosin ii result dominant character mutant heavy chain myh9 human disease model site-directed mutagenesis myoii myh9 excellent bait parent mutation myh9-like mutation rhoa mutation melanogaster behave amino acid substitution genetic interactors dominant characteristic wild-type genetic background zip myoii heavy chain drosophila melanogaster myosin rod r1171c melanogaster nonmuscle myosin ii certain hypomorphic allele sensitized genetic background human disease-causing dominant phenotype mendelian expectation partial wild-type function
