Mutations affecting thymus organogenesis in Medaka, Oryzias latipes.
The thymus is an organ for T lymphocyte maturation and is indispensable for the establishment of a highly developed immune system in vertebrates. In order to genetically dissect thymus organogenesis, we carried out a large-scale mutagenesis screening for Medaka mutations affecting recombination activating gene 1 (rag1) expression in the developing thymus. We identified 24 mutations, defining at least 13 genes, which led to a marked reduction of rag1 expression in the thymus. As thymus development depends on pharyngeal arches, we classified those mutations into three classes according to the defects in the pharyngeal arches. Class 1 mutants had no or slight morphological abnormalities in the pharyngeal arches, implying that the mutations may include defects in such thymus-specific events as lymphocyte development and thymic epithelial cell maturation. Class 2 mutants had abnormally shaped pharyngeal arches. Class 3 mutants showed severely attenuated pharyngeal arch development. In Class 2 and Class 3 mutants, the defects in thymus development may be due to abnormal pharyngeal arch development. Those mutations are expected to be useful for identifying the molecular mechanisms underlying thymus organogenesis.
Iwanami
Norimasa
N
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Takahama
Yousuke
Y
Kunimatsu
Sanae
S
Li
Jie
J
Takei
Rie
R
Ishikura
Yuko
Y
Suwa
Hiroshi
H
Niwa
Katsutoshi
K
Sasado
Takao
T
Morinaga
Chikako
C
Yasuoka
Akihito
A
Deguchi
Tomonori
T
Hirose
Yukihiro
Y
Yoda
Hiroki
H
Henrich
Thorsten
T
Ohara
Osamu
O
Kondoh
Hisato
H
Furutani-Seiki
Makoto
M
D000818:Animals; D001934:Branchial Region / Q000002:abnormalities / Q000196:embryology; D015870:Gene Expression / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D016654:Genes, RAG-1 / Q000502:physiology; D009154:Mutation; D009990:Oryzias / Q000002:abnormalities / Q000196:embryology* / Q000235:genetics*; D013950:Thymus Gland / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism