1. Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria
- Author
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Yukihiro Hirose, Akihito Yasuoka, Hiroshi Nishina, Felix Loosli, Hiroshi Suwa, Clemens Grabher, Katsutoshi Niwa, Satoshi Asaka, Hiroki Yoda, Takao Sasado, Kota Saito, Rebecca Quiring, Matthias Carl, Sanae Kunimatsu, Keiko Abe, Daiju Kitagawa, Tomonori Deguchi, Chikako Morinaga, Thorsten Henrich, Masakazu Osakada, Sylke Winkler, Tomomi Watanabe, Ryumei Kurashige, Katsuhito Takahashi, Yousuke Takahama, Hisato Kondoh, Joachim Wittbrodt, Toshiaki Katada, Norimasa Iwanami, Makoto Furutani-Seiki, and Filippo Del Bene
- Subjects
Genetics ,Mutation ,Embryology ,Liver morphogenesis ,Endoderm ,Mutant ,Oryzias ,Gallbladder ,Mutagenesis (molecular biology technique) ,Biology ,Lipid Metabolism ,medicine.disease_cause ,Phenotype ,Complementation ,Liver ,Endoderm formation ,medicine ,Animals ,Gene ,In Situ Hybridization ,Body Patterning ,Developmental Biology - 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.
- Published
- 2004
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