Research Project
Grant-in-Aid for Scientific Research (B)
The liver is an organ with vital functions, including processing and storage of nutrients, maintenance of serum composition, detoxification and bile production. Recently, several genes that are crucial for liver formation and function have been isolated in mice and confirmed by reverse genetics. Although a reverse genetic approach is powerful in characterizing function of known genes, knowledge of genes in liver formation and disease is still limited. Therefore, identifying mutations affecting these aspects will uncover genes required for these processes. Systematic forward genetic screens for mutations affecting liver formation and function such as hepatic bud formation, liver morphogenesis, bile color in the gall bladder, lipid metabolism, and liver laterality have been carried out in Medaka, Oryzias latipes. To isolate mutants that model human liver diseases, we are analyzing these mutations. Among them, kendama (ken) mutation was isolated as a gene that affects the laterality of the liver. ken mutant was viable and fertile with inverted positions of liver and heart, and with inverted spiral of gut. Interestingly, the spleen was almost lost in ken mutant. This phenotype is very similar to human genetic disease 'asplenia' whose gene mutation is still unknown. Furthermore, white livers consisting of bloated and Oil red O-positive hepatocytes were observed in ken mutants. Thus, ken mutation models human disease asplenia and Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). Especially, NAFLD and NASH are serious human diseases in the modern world, so ken mutation may shed a new light on the molecular mechanisms of these diseases and the preventive medicine.
All 2008 2007 2006 Other
All Journal Article (15 results) (of which Peer Reviewed: 4 results) Presentation (1 results) Remarks (2 results)
Cell Death Differ. 15
Pages: 89-93
Cell Death Differ 15
Develop. Growth Differ. 49
Pages: 163-170
Mol. Cell. Biol. 27
Pages: 5514-5522
Develop. Growth Differ 49
Mol. Cell. Biol 27
Cell 130
Pages: 811-923
Cell Tissue Res 327
Pages: 463-470
EMBO J. 25
Pages: 3286-3297
Cell Tissue Res. 323
Pages: 221-231
Proteomics 6
Pages: 2564-2570
Proc Natl Acad Sci USA. 103
Pages: 224-229
Endocrine J. 53
Pages: 157-172
細胞工学 25
Pages: 1178-1179
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