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