title: Human myo-inositol monophosphatase 2 rescues the nematode thermotaxis mutant ttx-7 more efficiently than IMPA1: functional and evolutionary considerations of the two mammalian myo-inositol monophosphatase genes.
abstract: Mammals express two myo-inositol monophosphatase (IMPase) genes, IMPA1/Impa1 and IMPA2/Impa2. In this study, we compared the spatial expression patterns of the two IMPase gene transcripts and proteins in mouse tissues. Results indicated discrete expression of the two IMPase genes and their protein products in various organs, including the brain. In Caenorhabditis elegans, loss of the IMPase gene, ttx-7, disrupts cellular polarity in RIA neurons, eliciting abnormal thermotaxis behavior. We performed a rescue experiment in mutant nematodes using mammalian IMPases. Human IMPA2 rescued the abnormal behavioral phenotype in the ttx-7 mutants more efficiently than IMPA1. These results raise a question about the phylogenetic origin of IMPases and the biological roles of mammalian IMPase 2 in mammals. Impa2 knockout mice generated in our laboratory, exhibited neither behavioral abnormalities nor a significant reduction in myo-inositol content in the brain and other examined tissues. Given the ability of human IMPA2 to rescue the ttx-7 mutant, and its genetic association with multiple neuropsychiatric disorders, close scrutiny of IMPA2 function and the evolutionary origin of IMPase genes is warranted.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan. tohnishi@brain.riken.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tanizawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Watanabe
authors.forename: Takemichi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hisako
authors.initials: H
authors.lastname: Ohba
authors.forename: Haruna
authors.initials: H
authors.lastname: Hirata
authors.forename: Chizu
authors.initials: C
authors.lastname: Kaneda
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Takafumi
authors.initials: T
authors.lastname: Arimoto
authors.forename: Kazutada
authors.initials: K
authors.lastname: Watanabe
authors.forename: Ikue
authors.initials: I
authors.lastname: Mori
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005075:Biological Evolution; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D059467:Transcriptome
chemical_list: D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase