Establishment and characterization of Roberts syndrome and SC phocomelia model medaka (Oryzias latipes).
Roberts syndrome and SC phocomelia (RBS/SC) are genetic autosomal recessive syndromes caused by establishment of cohesion 1 homolog 2 ( ESCO 2) mutation. RBS/SC appear to have a variety of clinical features, even with the same mutation of the ESCO2 gene. Here, we established and genetically characterized a medaka model of RBS/SC by reverse genetics. The RBS/SC model was screened from a mutant medaka library produced by the Targeting Induced Local Lesions in Genomes method. The medaka mutant carrying the homozygous mutation at R80S in the conserved region of ESCO2 exhibited clinical variety (i.e. developmental arrest with craniofacial and chromosomal abnormalities and embryonic lethality) as characterized in RBS/SC. Moreover, widespread apoptosis and downregulation of some gene expression, including notch1a, were detected in the R80S mutant. The R80S mutant is the animal model for RBS/SC and a valuable resource that provides the opportunity to extend knowledge of ESCO2. Downregulation of some gene expression in the R80S mutant is an important clue explaining non-correlation between genotype and phenotype in RBS/SC.
Department of Developmental Medicine, Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi, Osaka, Japan. morita-a@suzuka-u.ac.jp
Akihiro
A
Morita
Kumiko
K
Nakahira
Taeko
T
Hasegawa
Kaoru
K
Uchida
Yoshihito
Y
Taniguchi
Shunichi
S
Takeda
Atsushi
A
Toyoda
Yoshiyuki
Y
Sakaki
Atsuko
A
Shimada
Hiroyuki
H
Takeda
Itaru
I
Yanagihara
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003001:Cloning, Molecular; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004480:Ectromelia / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006972:Hypertelorism / Q000235:genetics* / Q000378:metabolism; D009990:Oryzias / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051881:Receptor, Notch1 / Q000096:biosynthesis; D059386:Reverse Genetics
D051881:Receptor, Notch1; D000123:Acetyltransferases