title: Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria.
abstract: We report here mutations affecting various aspects of liver development and function identified by multiple assays in a systematic mutagenesis screen in Medaka. The 22 identified recessive mutations assigned to 19 complementation groups fell into five phenotypic groups. Group 1, showing defective liver morphogenesis, comprises mutations in four genes, which may be involved in the regulation of growth or patterning of the gut endoderm. Group 2 comprises mutations in three genes that affect the laterality of the liver; in kendama mutants of this group, the laterality of the heart and liver is uncoupled and randomized. Group 3 includes mutations in three genes altering bile color, indicative of defects in hemoglobin-bilirubin metabolism and globin synthesis. Group 4 consists of mutations in three genes, characterized by a decrease in the accumulation of fluorescent metabolite of a phospholipase A(2) substrate, PED6, in the gall bladder. Lipid metabolism or the transport of lipid metabolites may be affected by these mutations. Mutations in Groups 3 and 4 may provide animal models for relevant human diseases. Group 5 mutations in six genes affect the formation of endoderm, endodermal rods and hepatic bud from which the liver develops. These Medaka mutations, identified by morphological and metabolite marker screens, should provide clues to understanding molecular mechanisms underlying formation of a functional liver.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asaka
authors.forename: Daiju
authors.initials: D
authors.lastname: Kitagawa
authors.forename: Kota
authors.initials: K
authors.lastname: Saito
authors.forename: Ryumei
authors.initials: R
authors.lastname: Kurashige
authors.forename: Takao
authors.initials: T
authors.lastname: Sasado
authors.forename: Chikako
authors.initials: C
authors.lastname: Morinaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suwa
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Niwa
authors.forename: Thorsten
authors.initials: T
authors.lastname: Henrich
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hirose
authors.forename: Akihito
authors.initials: A
authors.lastname: Yasuoka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoda
authors.forename: Tomonori
authors.initials: T
authors.lastname: Deguchi
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwanami
authors.forename: Sanae
authors.initials: S
authors.lastname: Kunimatsu
authors.forename: Masakazu
authors.initials: M
authors.lastname: Osakada
authors.forename: Felix
authors.initials: F
authors.lastname: Loosli
authors.forename: Rebecca
authors.initials: R
authors.lastname: Quiring
authors.forename: Matthias
authors.initials: M
authors.lastname: Carl
authors.forename: Clemens
authors.initials: C
authors.lastname: Grabher
authors.forename: Sylke
authors.initials: S
authors.lastname: Winkler
authors.forename: Filippo
authors.initials: F
authors.lastname: Del Bene
authors.forename: Joachim
authors.initials: J
authors.lastname: Wittbrodt
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishina
authors.forename: Hisato
authors.initials: H
authors.lastname: Kondoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Furutani-Seiki
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004707:Endoderm; D005704:Gallbladder / Q000378:metabolism; D017403:In Situ Hybridization; D050356:Lipid Metabolism; D008099:Liver / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology; D009154:Mutation; D009990:Oryzias / Q000196:embryology* / Q000235:genetics* / Q000502:physiology