title: Minos-insertion mutant of the Drosophila GBA gene homologue showed abnormal phenotypes of climbing ability, sleep and life span with accumulation of hydroxy-glucocerebroside.
abstract: Gaucher's disease in humans is considered a deficiency of glucocerebrosidase (GlcCerase) that result in the accumulation of its substrate, glucocerebroside (GlcCer). Although mouse models of Gaucher's disease have been reported from several laboratories, these models are limited due to the perinatal lethality of GlcCerase gene. Here, we examined phenotypes of Drosophila melanogaster homologues genes of the human Gaucher's disease gene by using Minos insertion. One of two Minos insertion mutants to unknown function gene (CG31414) accumulates the hydroxy-GlcCer in whole body of Drosophila melanogaster. This mutant showed abnormal phenotypes of climbing ability and sleep, and short lifespan. These abnormal phenotypes are very similar to that of Gaucher's disease in human. In contrast, another Minos insertion mutant (CG31148) and its RNAi line did not show such severe phenotype as observed in CG31414 gene mutation. The data suggests that Drosophila CG31414 gene mutation might be useful for unraveling the molecular mechanism of Gaucher's disease.
authors.affiliation: Foundation for Advancement of International Science, 24-16, Kasuga, 3-chome, Tsukuba, Ibaraki 305-0821, Japan; Ishida Group of Clock Gene, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan. Electronic address: kawasaki@fais.or.jp.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Foundation for Advancement of International Science, 24-16, Kasuga, 3-chome, Tsukuba, Ibaraki 305-0821, Japan; Ishida Group of Clock Gene, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan; Shigray Inc., Tsuchiura, Ibaraki 300-0876, Japan. Electronic address: suzuki-t@aist.go.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Foundation for Advancement of International Science, 24-16, Kasuga, 3-chome, Tsukuba, Ibaraki 305-0821, Japan; Ishida Group of Clock Gene, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8576, Japan.
authors.forename: Kumpei
authors.initials: K
authors.lastname: Ito
authors.affiliation: Ishida Group of Clock Gene, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8576, Japan. Electronic address: takahara.tsubasa.xd@aumni.tsukuba.ac.jp.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Takahara
authors.affiliation: Graduate School of Health Promotion Sciences, Tokyo Metropolitan University, Hachioji 192-0397, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Goto-Inoue
authors.affiliation: Department of Cell Biology and Anatomy, School of Medicine, Hamamatsu University, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address: setou@hama-med.ac.jp.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Foundation for Advancement of International Science, 24-16, Kasuga, 3-chome, Tsukuba, Ibaraki 305-0821, Japan; Ishida Group of Clock Gene, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8576, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Foundation for Advancement of International Science, 24-16, Kasuga, 3-chome, Tsukuba, Ibaraki 305-0821, Japan; Ishida Group of Clock Gene, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8576, Japan. Electronic address: n.ishida@aist.go.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Ishida
mesh_terms: D004251:DNA Transposable Elements / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005776:Gaucher Disease / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D009043:Motor Activity / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D005963:Glucosylceramides; D007527:Isoenzymes; D005962:Glucosylceramidase
keywords: Drosophila melanogaster; Gaucher's disease; Glucocerebrosidase; Life span; Neurodegenerative disease; Sleep