Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria |
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Authors: | Watanabe Tomomi Asaka Satoshi Kitagawa Daiju Saito Kota Kurashige Ryumei Sasado Takao Morinaga Chikako Suwa Hiroshi Niwa Katsutoshi Henrich Thorsten Hirose Yukihiro Yasuoka Akihito Yoda Hiroki Deguchi Tomonori Iwanami Norimasa Kunimatsu Sanae Osakada Masakazu Loosli Felix Quiring Rebecca Carl Matthias Grabher Clemens Winkler Sylke Del Bene Filippo Wittbrodt Joachim Abe Keiko Takahama Yousuke Takahashi Katsuhito Katada Toshiaki Nishina Hiroshi Kondoh Hisato Furutani-Seiki Makoto |
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Institution: | Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan. |
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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. |
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